Multitargeting: An Alternative Approach to Tackle Multidrug Resistance in Tuberculosis

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Abstract

Background: The prevalence of drug-resistant organisms has steadily increased over the past few decades worldwide. Especially in tuberculosis (TB) disease, the problems of co-morbidity and the rapid emergence of multidrug resistance have necessitated the development of multitarget-based therapeutic regimens. Several multitargeting compounds against Mycobacterium tuberculosis (Mtb) have been studied through novel in silico tools but these have rendered reduced efficacy in clinical trials. The authors have focussed on many exotic targets belonging to crucial Mtb survival pathways whose molecular structures and functions are underexplored. Likewise, insights into the hidden possibilities of promiscuous compounds from natural products or repurposed drugs to inhibit other cellular proteins apart from their validated targets are also depicted in this review. In addition to the existing line of drugs currently recommended for multidrug-resistant TB, newer host-directed therapies could also be fruitful. Furthermore, several challenges, including safety/efficacy ratios of multitarget compounds highlighted here, can also be circumnavigated by researchers to design “smart drugs” for improved tuberculosis therapeutics.

Conclusion: A holistic approach towards alleviating the existing drawbacks of drug discovery in drug-resistant TB has been outlined. Finally, considering the current needs, the authors have put forward an overall summary of possible trends in multitargeting that are significant for futuristic therapeutic solutions.

Graphical Abstract

[1]
Global Tuberculosis Report. World Health Organization 2021.
[2]
Allué-Guardia A, García JI, Torrelles JB. Evolution of drug-resistant Mycobacterium tuberculosis strains and their adaptation to the human lung environment. Front Microbiol 2021; 12: 612675.
[http://dx.doi.org/10.3389/fmicb.2021.612675] [PMID: 33613483]
[3]
Stephanie F, Saragih M, Tambunan USF. Recent progress and challenges for drug-resistant tuberculosis treatment. Pharmaceutics 2021; 13(5): 592.
[http://dx.doi.org/10.3390/pharmaceutics13050592] [PMID: 33919204]
[4]
Gray DA, Wenzel M. Multitarget approaches against multiresistant superbugs. ACS Infect Dis 2020; 6(6): 1346-65.
[http://dx.doi.org/10.1021/acsinfecdis.0c00001] [PMID: 32156116]
[5]
Li K, Schurig-Briccio LA, Feng X, et al. Multitarget drug discovery for tuberculosis and other infectious diseases. J Med Chem 2014; 57(7): 3126-39.
[http://dx.doi.org/10.1021/jm500131s] [PMID: 24568559]
[6]
Seung KJ, Keshavjee S, Rich ML. Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Cold Spring Harb Perspect Med 2015; 5(9): a017863.
[http://dx.doi.org/10.1101/cshperspect.a017863] [PMID: 25918181]
[7]
Li W, Upadhyay A, Fontes FL, et al. Novel insights into the mechanism of inhibition of MmpL3, a target of multiple pharmacophores in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2014; 58(11): 6413-23.
[http://dx.doi.org/10.1128/AAC.03229-14] [PMID: 25136022]
[8]
Harrison J, Cox JAG. Changing the rules of TB-drug discovery. J Med Chem 2019; 62(23): 10583-5.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01716] [PMID: 31664826]
[9]
Makhoba XH, Viegas C Jr, Mosa RA, Viegas FPD, Pooe OJ. Potential impact of the multi-target drug approach in the treatment of some complex diseases. Drug Des Devel Ther 2020; 14: 3235-49.
[http://dx.doi.org/10.2147/DDDT.S257494] [PMID: 32884235]
[10]
Ramsay RR, Popovic-Nikolic MR, Nikolic K, Uliassi E, Bolognesi ML. A perspective on multi‐target drug discovery and design for complex diseases. Clin Transl Med 2018; 7(1): 3.
[http://dx.doi.org/10.1186/s40169-017-0181-2] [PMID: 29340951]
[11]
Mase SR, Chorba T. Treatment of drug-resistant tuberculosis. Clin Chest Med 2019; 40(4): 775-95.
[http://dx.doi.org/10.1016/j.ccm.2019.08.002] [PMID: 31731984]
[12]
Bolognesi ML, Cavalli A. Multitarget drug discovery and polypharmacology. ChemMedChem 2016; 11(12): 1190-2.
[http://dx.doi.org/10.1002/cmdc.201600161] [PMID: 27061625]
[13]
Singh R, Dwivedi SP, Gaharwar US, Meena R, Rajamani P, Prasad T. Recent updates on drug resistance in Mycobacterium tuberculosis. J Appl Microbiol 2020; 128(6): 1547-67.
[http://dx.doi.org/10.1111/jam.14478] [PMID: 31595643]
[14]
Lopez Quezada L, Li K, McDonald SL, et al. Dual-pharmacophore pyrithione-containing cephalosporins kill both replicating and nonreplicating Mycobacterium tuberculosis. ACS Infect Dis 2019; 5(8): 1433-45.
[http://dx.doi.org/10.1021/acsinfecdis.9b00112] [PMID: 31184461]
[15]
Black TA, Buchwald UK. The pipeline of new molecules and regimens against drug-resistant tuberculosis. J Clin Tuberc Other Mycobact Dis 2021; 25: 100285.
[http://dx.doi.org/10.1016/j.jctube.2021.100285] [PMID: 34816020]
[16]
Khoshnood S, Goudarzi M, Taki E, et al. Bedaquiline: Current status and future perspectives. J Glob Antimicrob Resist 2021; 25: 48-59.
[http://dx.doi.org/10.1016/j.jgar.2021.02.017] [PMID: 33684606]
[17]
Boldrin F, Provvedi R, Cioetto Mazzabò L, Segafreddo G, Manganelli R. Tolerance and persistence to drugs: A main challenge in the fight against Mycobacterium tuberculosis. Front Microbiol 2020; 11: 1924.
[http://dx.doi.org/10.3389/fmicb.2020.01924] [PMID: 32983003]
[18]
Amaral L, Viveiros M. Thioridazine: A non-antibiotic drug highly effective, in combination with first line anti-tuberculosis drugs, against any form of antibiotic resistance of Mycobacterium tuberculosis due to its multi-mechanisms of action. Antibiotics 2017; 6(1): 3.
[http://dx.doi.org/10.3390/antibiotics6010003] [PMID: 28098814]
[19]
Boshoff HIM, Barry CE III. Tuberculosis - metabolism and respiration in the absence of growth. Nat Rev Microbiol 2005; 3(1): 70-80.
[http://dx.doi.org/10.1038/nrmicro1065] [PMID: 15608701]
[20]
Hartman TE, Wang Z, Jansen RS, Gardete S, Rhee KY. Metabolic perspectives on persistence. Microbiol Spectr 2017; 5(1): 5.1.16.
[http://dx.doi.org/10.1128/microbiolspec.TBTB2-0026-2016] [PMID: 28155811]
[21]
Lupoli TJ, Vaubourgeix J, Burns-Huang K, Gold B. Targeting the proteostasis network for mycobacterial drug discovery. ACS Infect Dis 2018; 4(4): 478-98.
[http://dx.doi.org/10.1021/acsinfecdis.7b00231] [PMID: 29465983]
[22]
Early J, Ollinger J, Darby C, et al. Identification of compounds with ph-dependent bactericidal activity against Mycobacterium tuberculosis. ACS Infect Dis 2019; 5(2): 272-80.
[http://dx.doi.org/10.1021/acsinfecdis.8b00256] [PMID: 30501173]
[23]
Santucci P, Greenwood DJ, Fearns A, Chen K, Jiang H, Gutierrez MG. Intracellular localisation of Mycobacterium tuberculosis affects efficacy of the antibiotic pyrazinamide. Nat Commun 2021; 12(1): 3816.
[http://dx.doi.org/10.1038/s41467-021-24127-3] [PMID: 34155215]
[24]
Bhat ZS, Rather MA, Maqbool M, Lah HUL, Yousuf SK, Ahmad Z. Cell wall: A versatile fountain of drug targets in Mycobacterium tuberculosis. Biomed Pharmacother 2017; 95: 1520-34.
[http://dx.doi.org/10.1016/j.biopha.2017.09.036] [PMID: 28946393]
[25]
Bhat ZS, Rather MA, Maqbool M, Ahmad Z. Drug targets exploited in Mycobacterium tuberculosis: Pitfalls and promises on the horizon. Biomed Pharmacother 2018; 103: 1733-47.
[http://dx.doi.org/10.1016/j.biopha.2018.04.176] [PMID: 29864964]
[26]
Wellington S, Hung DT. The expanding diversity of mycobacterium tuberculosis drug targets. ACS Infect Dis 2018; 4(5): 696-714.
[http://dx.doi.org/10.1021/acsinfecdis.7b00255] [PMID: 29412643]
[27]
Consalvi S, Scarpecci C, Biava M, Poce G. Mycobacterial tryptophan biosynthesis: A promising target for tuberculosis drug development? Bioorg Med Chem Lett 2019; 29(23): 126731.
[http://dx.doi.org/10.1016/j.bmcl.2019.126731] [PMID: 31627992]
[28]
Shetye GS, Franzblau SG, Cho S. New tuberculosis drug targets, their inhibitors, and potential therapeutic impact. Transl Res 2020; 220: 68-97.
[http://dx.doi.org/10.1016/j.trsl.2020.03.007] [PMID: 32275897]
[29]
Thanna S, Sucheck SJ. Targeting the trehalose utilization pathways of Mycobacterium tuberculosis. Med Chem Comm 2016; 7(1): 69-85.
[http://dx.doi.org/10.1039/C5MD00376H] [PMID: 26941930]
[30]
Kapil S, Petit C, Drago VN, Ronning DR, Sucheck SJ. Synthesis and in vitro characterization of trehalose-based inhibitors of mycobacterial trehalose 6-phosphate phosphatases. Chem Bio Chem 2019; 20(2): 260-9.
[http://dx.doi.org/10.1002/cbic.201800551] [PMID: 30402996]
[31]
Liu C, Dunaway-Mariano D, Mariano PS. Rational design of reversible inhibitors for trehalose 6-phosphate phosphatases. Eur J Med Chem 2017; 128: 274-86.
[http://dx.doi.org/10.1016/j.ejmech.2017.02.001] [PMID: 28192710]
[32]
Korte J, Alber M, Trujillo CM, et al. Trehalose-6-phosphate-mediated toxicity determines essentiality of otsb2 in mycobacterium tuberculosisin vitro and in mice. PLoS Pathog 2016; 12(12): e1006043.
[http://dx.doi.org/10.1371/journal.ppat.1006043] [PMID: 27936238]
[33]
Murphy HN, Stewart GR, Mischenko VV, et al. The OtsAB pathway is essential for trehalose biosynthesis in Mycobacterium tuberculosis. J Biol Chem 2005; 280(15): 14524-9.
[http://dx.doi.org/10.1074/jbc.M414232200] [PMID: 15703182]
[34]
Pan YT, Carroll JD, Elbein AD. Trehalose-phosphate synthase of Mycobacterium tuberculosis. Eur J Biochem 2002; 269(24): 6091-100.
[http://dx.doi.org/10.1046/j.1432-1033.2002.03327.x] [PMID: 12473104]
[35]
Mendes V, Acebrón-García-de-Eulate M, Verma N, Blaszczyk M, Dias MVB, Blundell TL. Mycobacterial OtsA structures unveil substrate preference mechanism and allosteric regulation by 2-oxoglutarate and 2-phosphoglycerate. MBio 2019; 10(6): e02272-19.
[http://dx.doi.org/10.1128/mBio.02272-19] [PMID: 31772052]
[36]
Kalscheuer R, Weinrick B, Veeraraghavan U, Besra GS, Jacobs WR Jr. Trehalose-recycling ABC transporter LpqY-SugA-SugB-SugC is essential for virulence of Mycobacterium tuberculosis. Proc Natl Acad Sci 2010; 107(50): 21761-6.
[http://dx.doi.org/10.1073/pnas.1014642108] [PMID: 21118978]
[37]
Veleti SK, Lindenberger JJ, Thanna S, Ronning DR, Sucheck SJ. Synthesis of a poly-hydroxypyrolidine-based inhibitor of Mycobacterium tuberculosis GlgE. J Org Chem 2014; 79(20): 9444-50.
[http://dx.doi.org/10.1021/jo501481r] [PMID: 25137149]
[38]
Ma Y, Stern RJ, Scherman MS, et al. Drug targeting Mycobacterium tuberculosis cell wall synthesis: genetics of dTDP-rhamnose synthetic enzymes and development of a microtiter plate-based screen for inhibitors of conversion of dTDP-glucose to dTDP-rhamnose. Antimicrob Agents Chemother 2001; 45(5): 1407-16.
[http://dx.doi.org/10.1128/AAC.45.5.1407-1416.2001] [PMID: 11302803]
[39]
Ma Y, Pan F, McNeil M. Formation of dTDP-rhamnose is essential for growth of mycobacteria. J Bacteriol 2002; 184(12): 3392-5.
[http://dx.doi.org/10.1128/JB.184.12.3392-3395.2002] [PMID: 12029057]
[40]
Wang Y, Hess TN, Jones V, Zhou JZ, McNeil MR, Andrew McCammon J. Novel inhibitors of Mycobacterium tuberculosis dTDP-6-deoxy-l-lyxo-4-hexulose reductase (RmlD) identified by virtual screening. Bioorg Med Chem Lett 2011; 21(23): 7064-7.
[http://dx.doi.org/10.1016/j.bmcl.2011.09.094] [PMID: 22014548]
[41]
Sivendran S, Jones V, Sun D, et al. Identification of triazinoindol-benzimidazolones as nanomolar inhibitors of the Mycobacterium tuberculosis enzyme TDP-6-deoxy-d-xylo-4-hexopyranosid-4-ulose 3,5-epimerase (RmlC). Bioorg Med Chem 2010; 18(2): 896-908.
[http://dx.doi.org/10.1016/j.bmc.2009.11.033] [PMID: 19969466]
[42]
Babaoglu K, Page MA, Jones VC, et al. Novel inhibitors of an emerging target in Mycobacterium tuberculosis; substituted thiazolidinones as inhibitors of dTDP-rhamnose synthesis. Bioorg Med Chem Lett 2003; 13(19): 3227-30.
[http://dx.doi.org/10.1016/S0960-894X(03)00673-5] [PMID: 12951098]
[43]
Ren JX, Qian HL, Huang YX, Zhu NY, Si SY, Xie Y. Virtual screening for the identification of novel inhibitors of Mycobacterium tuberculosis cell wall synthesis: Inhibitors targeting RmlB and RmlC. Comput Biol Med 2015; 58: 110-7.
[http://dx.doi.org/10.1016/j.compbiomed.2014.12.020] [PMID: 25637777]
[44]
Mansuri R, Ansari MY, Singh J, et al. Computational elucidation of structural basis for ligand binding with mycobacterium tuberculosis glucose-1-phosphate thymidylyltransferase (RmlA). Curr Pharm Biotechnol 2016; 17(12): 1089-99.
[http://dx.doi.org/10.2174/1389201017666160909155959] [PMID: 27633891]
[45]
Harathi N, Pulaganti M, Anuradha CM, Kumar Chitta S. Inhibition of Mycobacterium-RmlA by molecular modeling, dynamics simulation, and docking. Adv Bioinforma 2016; 2016: 1-13.
[http://dx.doi.org/10.1155/2016/9841250] [PMID: 26981117]
[46]
Shefin B, Bindu A. Virtual screening for identifying a putative inhibitor of rmlc a major target protein in tuberculosis disease. Int J Pharm Biol Sci 2015; 6(4): B616-28.
[47]
Mills JA, Motichka K, Jucker M, et al. Inactivation of the mycobacterial rhamnosyltransferase, which is needed for the formation of the arabinogalactan-peptidoglycan linker, leads to irreversible loss of viability. J Biol Chem 2004; 279(42): 43540-6.
[http://dx.doi.org/10.1074/jbc.M407782200] [PMID: 15294902]
[48]
Wu Q, Zhou P, Qian S, et al. Cloning, expression, identification and bioinformatics analysis of Rv3265c gene from Mycobacterium tuberculosis in Escherichia coli. Asian Pac J Trop Med 2011; 4(4): 266-70.
[http://dx.doi.org/10.1016/S1995-7645(11)60083-7] [PMID: 21771467]
[49]
Munshi T, Gupta A, Evangelopoulos D, et al. Characterisation of ATP-dependent Mur ligases involved in the biogenesis of cell wall peptidoglycan in Mycobacterium tuberculosis. PLoS One 2013; 8(3): e60143.
[http://dx.doi.org/10.1371/journal.pone.0060143] [PMID: 23555903]
[50]
Eniyan K, Rani J, Ramachandran S, Bhat R, Khan IA, Bajpai U. Screening of antitubercular compound library identifies inhibitors of mur enzymes in Mycobacterium tuberculosis. SLAS Discov 2020; 25(1): 70-8.
[http://dx.doi.org/10.1177/2472555219881148] [PMID: 31597510]
[51]
Catalão MJ, Filipe SR, Pimentel M. Revisiting anti-tuberculosis therapeutic strategies that target the peptidoglycan structure and synthesis. Front Microbiol 2019; 10: 190.
[http://dx.doi.org/10.3389/fmicb.2019.00190] [PMID: 30804921]
[52]
Arvind A, Kumar V, Saravanan P, Mohan CG. Homology modeling, molecular dynamics and inhibitor binding study on MurD ligase of Mycobacterium tuberculosis. Interdiscip Sci 2012; 4(3): 223-38.
[http://dx.doi.org/10.1007/s12539-012-0133-x] [PMID: 23292696]
[53]
Kumar P, Saumya KU, Giri R. Identification of peptidomimetic compounds as potential inhibitors against MurA enzyme of Mycobacterium tuberculosis. J Biomol Struct Dyn 2020; 38(17): 4997-5013.
[http://dx.doi.org/10.1080/07391102.2019.1696231] [PMID: 31755364]
[54]
Singh S, Bajpai U, Michael Lynn A. Structure based virtual screening to identify inhibitors against MurE enzyme of Mycobacterium tuberculosis using AutoDock Vina. Bioinformation 2014; 10(11): 697-702.
[http://dx.doi.org/10.6026/97320630010697] [PMID: 25512687]
[55]
Guzman JD, Pesnot T, Barrera DA, et al. Tetrahydroisoquinolines affect the whole-cell phenotype of Mycobacterium tuberculosis by inhibiting the ATP-dependent MurE ligase. J Antimicrob Chemother 2015; 70(6): 1691-703.
[http://dx.doi.org/10.1093/jac/dkv010] [PMID: 25656411]
[56]
Mikušová K, Huang H, Yagi T, et al. Decaprenylphosphoryl arabinofuranose, the donor of the D-arabinofuranosyl residues of mycobacterial arabinan, is formed via a two-step epimerization of decaprenylphosphoryl ribose. J Bacteriol 2005; 187(23): 8020-5.
[http://dx.doi.org/10.1128/JB.187.23.8020-8025.2005] [PMID: 16291675]
[57]
Manina G, Pasca MR, Buroni S, De Rossi E, Riccardi G. Decaprenylphosphoryl-β-D-ribose 2′-epimerase from Mycobacterium tuberculosis is a magic drug target. Curr Med Chem 2010; 17(27): 3099-108.
[http://dx.doi.org/10.2174/092986710791959693] [PMID: 20629622]
[58]
Bhutani I, Loharch S, Gupta P, Madathil R, Parkesh R. Structure, dynamics, and interaction of Mycobacterium tuberculosis (Mtb) DprE1 and DprE2 examined by molecular modeling, simulation, and electrostatic studies. PLoS One 2015; 10(3): e0119771.
[http://dx.doi.org/10.1371/journal.pone.0119771] [PMID: 25789990]
[59]
Piton J, Vocat A, Lupien A, et al. Structure-based drug design and characterization of sulfonyl-piperazine benzothiazinone inhibitors of dpre1 from Mycobacterium tuberculosis. Antimicrob Agents Chemother 2018; 62(10): e00681-18.
[http://dx.doi.org/10.1128/AAC.00681-18] [PMID: 30012754]
[60]
Piton J, Foo CSY, Cole ST. Structural studies of Mycobacterium tuberculosis DprE1 interacting with its inhibitors. Drug Discov Today 2017; 22(3): 526-33.
[http://dx.doi.org/10.1016/j.drudis.2016.09.014] [PMID: 27666194]
[61]
Gawad J, Bonde C. Decaprenyl-phosphoryl-ribose 2′-epimerase (DprE1): challenging target for antitubercular drug discovery. Chem Cent J 2018; 12(1): 72.
[http://dx.doi.org/10.1186/s13065-018-0441-2] [PMID: 29936616]
[62]
Korch SB, Malhotra V, Contreras H, Clark-Curtiss JE. The Mycobacterium tuberculosis relBE toxin:antitoxin genes are stress-responsive modules that regulate growth through translation inhibition. J Microbiol 2015; 53(11): 783-95.
[http://dx.doi.org/10.1007/s12275-015-5333-8] [PMID: 26502963]
[63]
Schuster CF, Bertram R. Toxin-antitoxin systems are ubiquitous and versatile modulators of prokaryotic cell fate. FEMS Microbiol Lett 2013; 340(2): 73-85.
[http://dx.doi.org/10.1111/1574-6968.12074] [PMID: 23289536]
[64]
Sala A, Bordes P, Genevaux P. Multiple toxin-antitoxin systems in Mycobacterium tuberculosis. Toxins (Basel) 2014; 6(3): 1002-20.
[http://dx.doi.org/10.3390/toxins6031002] [PMID: 24662523]
[65]
Keren I, Minami S, Rubin E, Lewis K. Characterization and transcriptome analysis of Mycobacterium tuberculosis persisters. MBio 2011; 2(3): e00100-11.
[http://dx.doi.org/10.1128/mBio.00100-11] [PMID: 21673191]
[66]
Slayden RA, Dawson CC, Cummings JE. Toxin–antitoxin systems and regulatory mechanisms in Mycobacterium tuberculosis. Pathog Dis 2018; 76(4): fty039.
[http://dx.doi.org/10.1093/femspd/fty039] [PMID: 29788125]
[67]
Sundar S, Rajan MP, Piramanayagam S. In silico derived peptides for inhibiting the toxin–antitoxin systems of mycobacterium tuberculosis: Basis for developing peptide-based therapeutics. Int J Pept Res Ther 2019; 25(4): 1467-75.
[http://dx.doi.org/10.1007/s10989-018-9792-8]
[68]
DeJesus MA, Gerrick ER, Xu W, et al. Comprehensive essentiality analysis of the Mycobacterium tuberculosis genome via saturating transposon mutagenesis. MBio 2017; 8(1): e02133-16.
[http://dx.doi.org/10.1128/mBio.02133-16] [PMID: 28096490]
[69]
Freire DM, Gutierrez C, Garza-Garcia A, et al. An NAD+ phosphorylase toxin triggers mycobacterium tuberculosis cell death. Mol Cell 2019; 73(6): 1282-1291.e8.
[http://dx.doi.org/10.1016/j.molcel.2019.01.028] [PMID: 30792174]
[70]
Zhai W, Wu F, Zhang Y, Fu Y, Liu Z. The immune escape mechanisms of Mycobacterium tuberculosis. Int J Mol Sci 2019; 20(2): 340.
[http://dx.doi.org/10.3390/ijms20020340] [PMID: 30650615]
[71]
Buchmeier NA, Newton GL, Koledin T, Fahey RC. Association of mycothiol with protection of Mycobacterium tuberculosis from toxic oxidants and antibiotics. Mol Microbiol 2003; 47(6): 1723-32.
[http://dx.doi.org/10.1046/j.1365-2958.2003.03416.x] [PMID: 12622824]
[72]
Trivedi A, Singh N, Bhat SA, Gupta P, Kumar A. Redox biology of tuberculosis pathogenesis. Adv Microb Physiol 2012; 60: 263-324.
[http://dx.doi.org/10.1016/B978-0-12-398264-3.00004-8] [PMID: 22633061]
[73]
Fan F, Vetting MW, Frantom PA, Blanchard JS. Structures and mechanisms of the mycothiol biosynthetic enzymes. Curr Opin Chem Biol 2009; 13(4): 451-9.
[http://dx.doi.org/10.1016/j.cbpa.2009.07.018] [PMID: 19699138]
[74]
Gutierrez-Lugo MT, Baker H, Shiloach J, Boshoff H, Bewley CA. Dequalinium, a new inhibitor of Mycobacterium tuberculosis mycothiol ligase identified by high-throughput screening. SLAS Discov 2009; 14(6): 643-52.
[http://dx.doi.org/10.1177/1087057109335743] [PMID: 19525487]
[75]
Kapnick SM, Zhang Y. New tuberculosis drug development: Targeting the shikimate pathway. Expert Opin Drug Discov 2008; 3(5): 565-77.
[http://dx.doi.org/10.1517/17460441.3.5.565] [PMID: 23484927]
[76]
Nunes JES, Duque MA, de Freitas TF, et al. Mycobacterium tuberculosis shikimate pathway enzymes as targets for the rational design of anti-tuberculosis drugs. Molecules 2020; 25(6): 1259.
[http://dx.doi.org/10.3390/molecules25061259] [PMID: 32168746]
[77]
Nirmal CR, Rao R, Hopper W. Inhibition of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis: In silico screening and in vitro validation. Eur J Med Chem 2015; 105: 182-93.
[http://dx.doi.org/10.1016/j.ejmech.2015.10.014] [PMID: 26491981]
[78]
Madhulitha NR, Kumar KS, Pasala C, Pakala S, Umamaheswari A. Identification of potential inhibitors for AroG against Mycobacterium tuberculosis. J Biomol Struct Dyn 2019; 37: 29-30.
[http://dx.doi.org/10.1080/07391102.2019.1604468]
[79]
Reichau S, Jiao W, Walker SR, Hutton RD, Baker EN, Parker EJ. Potent inhibitors of a shikimate pathway enzyme from Mycobacterium tuberculosis: Combining mechanism- and modeling-based design. J Biol Chem 2011; 286(18): 16197-207.
[http://dx.doi.org/10.1074/jbc.M110.211649] [PMID: 21454647]
[80]
Zhu N, Wang X, Li D, et al. IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis. Sci Rep 2018; 8(1): 17439.
[http://dx.doi.org/10.1038/s41598-018-35701-z] [PMID: 30487577]
[81]
Sivaranjani P, Naik VU, Madhulitha NR, et al. Design of novel antimycobacterial molecule targeting shikimate pathway of Mycobacterium tuberculosis. Indian J Pharm Sci 2019; 81(3): 438-47.
[http://dx.doi.org/10.36468/pharmaceutical-sciences.528]
[82]
Isa MA, Majumdhar RS, Haider S. In silico docking and molecular dynamics simulation of 3-dehydroquinate synthase (DHQS) from Mycobacterium tuberculosis. J Mol Model 2018; 24(6): 132.
[http://dx.doi.org/10.1007/s00894-018-3637-4] [PMID: 29752576]
[83]
Tizón L, Otero JM, Prazeres VFV, et al. A prodrug approach for improving antituberculosis activity of potent Mycobacterium tuberculosis type II dehydroquinase inhibitors. J Med Chem 2011; 54(17): 6063-84.
[http://dx.doi.org/10.1021/jm2006063] [PMID: 21780742]
[84]
Petersen GO, Saxena S, Renuka J, et al. Structure-based virtual screening as a tool for the identification of novel inhibitors against Mycobacterium tuberculosis 3-dehydroquinate dehydratase. J Mol Graph Model 2015; 60: 124-31.
[http://dx.doi.org/10.1016/j.jmgm.2015.05.001] [PMID: 26043661]
[85]
Lone MY, Athar M, Gupta VK, Jha PC. Prioritization of natural compounds against Mycobacterium tuberculosis 3-dehydroquinate dehydratase: A combined in-silico and in-vitro study. Biochem Biophys Res Commun 2017; 491(4): 1105-11.
[http://dx.doi.org/10.1016/j.bbrc.2017.08.020] [PMID: 28789944]
[86]
Dias MVB, Snee WC, Bromfield KM, et al. Structural investigation of inhibitor designs targeting 3-dehydroquinate dehydratase from the shikimate pathway of Mycobacterium tuberculosis. Biochem J 2011; 436(3): 729-39.
[http://dx.doi.org/10.1042/BJ20110002] [PMID: 21410435]
[87]
Miranda PHS, Lourenço EMG, Morais AMS, et al. Molecular modeling of a series of dehydroquinate dehydratase type II inhibitors of Mycobacterium tuberculosis and design of new binders. Mol Divers 2021; 25(1): 1-12.
[http://dx.doi.org/10.1007/s11030-019-10020-1] [PMID: 31820222]
[88]
Yao Y, Ze-Sheng L. Structure-and-mechanism-based design and discovery of type II Mycobacterium tuberculosis dehydroquinate dehydratase inhibitors. Curr Top Med Chem 2013; 14(1): 51-63.
[http://dx.doi.org/10.2174/1568026613666131113150257] [PMID: 24236726]
[89]
Souza JVP, Kioshima ES, Murase LS, et al. Identification of new putative inhibitors of Mycobacterium tuberculosis 3-dehydroshikimate dehydratase from a combination of ligand- and structure-based and deep learning in silico approaches. J Biomol Struct Dyn 2022; 1-10.
[http://dx.doi.org/10.1080/07391102.2022.2042389] [PMID: 35196960]
[90]
Deng Q, Meng J, Liu Y, Guan Y, Xiao C. IMB-SD62, a triazolothiadiazoles derivative with promising action against tuberculosis. Tuberculosis 2018; 112: 37-44.
[http://dx.doi.org/10.1016/j.tube.2018.07.006] [PMID: 30205967]
[91]
Gordon S, Simithy J, Goodwin DC, Calderón AI. Selective Mycobacterium tuberculosis shikimate kinase inhibitors as potential antibacterials. Perspect Medicin Chem 2015; 7: PMC.S13212.
[http://dx.doi.org/10.4137/PMC.S13212] [PMID: 25861218]
[92]
Mehra R, Rajput VS, Gupta M, et al. Benzothiazole derivative as a novel Mycobacterium tuberculosis shikimate kinase inhibitor: Identification and elucidation of its allosteric mode of inhibition. J Chem Inf Model 2016; 56(5): 930-40.
[http://dx.doi.org/10.1021/acs.jcim.6b00056] [PMID: 27149193]
[93]
Rajput VS, Mehra R, Kumar S, Nargotra A, Singh PP, Khan IA. Screening of antitubercular compound library identifies novel shikimate kinase inhibitors of Mycobacterium tuberculosis. Appl Microbiol Biotechnol 2016; 100(12): 5415-26.
[http://dx.doi.org/10.1007/s00253-015-7268-8] [PMID: 26887318]
[94]
Sahu PK, Raval MK. Virtual screening for inhibitors of shikimate kinase of Mycobacterium tuberculosis. Pharm Biol Eval 2016; 3: 320-6.
[95]
Simithy J, Fuanta NR, Alturki M, et al. Slow-binding inhibition of mycobacterium tuberculosis shikimate kinase by manzamine alkaloids. Biochemistry 2018; 57(32): 4923-33.
[http://dx.doi.org/10.1021/acs.biochem.8b00231] [PMID: 30063132]
[96]
Alturki MS, Fuanta NR, Jarrard MA, et al. A multifaceted approach to identify non-specific enzyme inhibition: Application to Mycobacterium tuberculosis shikimate kinase. Bioorg Med Chem Lett 2018; 28(4): 802-8.
[http://dx.doi.org/10.1016/j.bmcl.2017.12.002] [PMID: 29366649]
[97]
Parish T, Stoker NG. The common aromatic amino acid biosynthesis pathway is essential in Mycobacterium tuberculosis. Microbiology (Reading) 2002; 148(10): 3069-77.
[http://dx.doi.org/10.1099/00221287-148-10-3069] [PMID: 12368440]
[98]
Chaudhuri BN, Sawaya MR, Kim CY, et al. The crystal structure of the first enzyme in the pantothenate biosynthetic pathway, ketopantoate hydroxymethyltransferase, from M. tuberculosis. Structure 2003; 11(7): 753-64.
[http://dx.doi.org/10.1016/S0969-2126(03)00106-0] [PMID: 12842039]
[99]
Talevi A. Multi-target pharmacology: Possibilities and limitations of the “skeleton key approach” from a medicinal chemist perspective. Front Pharmacol 2015; 6: 205.
[http://dx.doi.org/10.3389/fphar.2015.00205] [PMID: 26441661]
[100]
Lage OM, Ramos MC, Calisto R, Almeida E, Vasconcelos V, Vicente F. Current screening methodologies in drug discovery for selected human diseases. Mar Drugs 2018; 16(8): 279.
[http://dx.doi.org/10.3390/md16080279]
[101]
Horman SR. Complex high-content phenotypic screening. In: Chen T, Chai SC, Eds. Special Topics in Drug Discovery. London: Intech Open 2016.
[http://dx.doi.org/10.5772/65387]
[102]
Katsila T, Spyroulias GA, Patrinos GP, Matsoukas MT. Computational approaches in target identification and drug discovery. Comput Struct Biotechnol J 2016; 14: 177-84.
[http://dx.doi.org/10.1016/j.csbj.2016.04.004] [PMID: 27293534]
[103]
Korcsmáros T, Szalay MS, Böde C, Kovács IA, Csermely P. How to design multi-target drugs. Expert Opin Drug Discov 2007; 2(6): 799-808.
[http://dx.doi.org/10.1517/17460441.2.6.799] [PMID: 23488998]
[104]
Bang S, Son S, Kim S, Shin H. Disease pathway cut for multi-target drugs. BMC Bioinformatics 2019; 20(1): 74.
[http://dx.doi.org/10.1186/s12859-019-2638-3] [PMID: 30760209]
[105]
Zhang W, Pei J, Lai L. Computational multitarget drug design. J Chem Inf Model 2017; 57(3): 403-12.
[http://dx.doi.org/10.1021/acs.jcim.6b00491] [PMID: 28166637]
[106]
Grzelak EM, Choules MP, Gao W, et al. Strategies in anti-Mycobacterium tuberculosis drug discovery based on phenotypic screening. J Antibiot 2019; 72(10): 719-28.
[http://dx.doi.org/10.1038/s41429-019-0205-9] [PMID: 31292530]
[107]
Ollinger J, Kumar A, Roberts DM, Bailey MA, Casey A, Parish T. A high-throughput whole cell screen to identify inhibitors of Mycobacterium tuberculosis. PLoS One 2019; 14(1): e0205479.
[http://dx.doi.org/10.1371/journal.pone.0205479] [PMID: 30650074]
[108]
Kubota K, Funabashi M, Ogura Y. Target deconvolution from phenotype-based drug discovery by using chemical proteomics approaches. Biochim Biophys Acta Proteins Proteomics 2019; 1867(1): 22-7.
[http://dx.doi.org/10.1016/j.bbapap.2018.08.002] [PMID: 30392561]
[109]
Zheng C, Guo Z, Huang C, et al. Large-scale direct targeting for drug repositioning and discovery. Sci Rep 2015; 5(1): 11970.
[http://dx.doi.org/10.1038/srep11970] [PMID: 26155766]
[110]
Wyatt PG, Gilbert IH, Read KD, Fairlamb AH. Target validation: Linking target and chemical properties to desired product profile. Curr Top Med Chem 2011; 11(10): 1275-83.
[http://dx.doi.org/10.2174/156802611795429185] [PMID: 21401506]
[111]
Chiarelli LR, Mori G, Orena BS, et al. A multitarget approach to drug discovery inhibiting Mycobacterium tuberculosis PyrG and PanK. Sci Rep 2018; 8(1): 3187.
[http://dx.doi.org/10.1038/s41598-018-21614-4] [PMID: 29453370]
[112]
Deng YH, Wang NN, Zou ZX, et al. Multi-target screening and experimental validation of natural products from Selaginella plants against Alzheimer’s disease. Front Pharmacol 2017; 8: 539.
[http://dx.doi.org/10.3389/fphar.2017.00539] [PMID: 28890698]
[113]
Raj S, Saha G, Sasidharan S, Dubey VK, Saudagar P. Biochemical characterization and chemical validation of Leishmania MAP Kinase-3 as a potential drug target. Sci Rep 2019; 9: 16209.
[http://dx.doi.org/10.1038/s41598-019-52774-6] [PMID: 31700105]
[114]
Tükenmez H, Edström I, Ummanni R, et al. Mycobacterium tuberculosis virulence inhibitors discovered by Mycobacterium marinum high-throughput screening. Sci Rep 2019; 9(1): 26.
[http://dx.doi.org/10.1038/s41598-018-37176-4] [PMID: 30631100]
[115]
Kingdon ADH, Alderwick LJ. Structure-based in silico approaches for drug discovery against Mycobacterium tuberculosis. Comput Struct Biotechnol J 2021; 19: 3708-19.
[http://dx.doi.org/10.1016/j.csbj.2021.06.034] [PMID: 34285773]
[116]
Yu W, MacKerell AD. Computer-aided drug design methods. In: Sass P, Ed. Antibiotics. New York: Humana Press 2017; 1520: pp. 85-106.
[http://dx.doi.org/10.1007/978-1-4939-6634-9_5]
[117]
Sánchez-Tejeda JF, Sánchez-Ruiz JF, Salazar JR, Loza-Mejía MA. A definition of “Multitargeticity”: Identifying potential multitarget and selective ligands through a vector analysis. Front Chem 2020; 8: 176.
[http://dx.doi.org/10.3389/fchem.2020.00176] [PMID: 32232029]
[118]
Viana JO, Félix MB, Maia MS, Serafim VL, Scotti L, Scotti MT. Drug discovery and computational strategies in the multitarget drugs era. Braz J Pharm Sci 2018; 54(spe): e01010.
[http://dx.doi.org/10.1590/s2175-97902018000001010]
[119]
Stelitano G, Sammartino JC, Chiarelli LR. Multitargeting compounds: A promising strategy to overcome multi-drug resistant tuberculosis. Molecules 2020; 25(5): 1239.
[http://dx.doi.org/10.3390/molecules25051239] [PMID: 32182964]
[120]
Foo CSY, Pethe K, Lupien A. Oxidative phosphorylation-an update on a new, essential target space for drug discovery in Mycobacterium tuberculosis. Appl Sci 2020; 10(7): 2339.
[http://dx.doi.org/10.3390/app10072339]
[121]
Feng X, Zhu W, Schurig-Briccio LA, et al. Antiinfectives targeting enzymes and the proton motive force. Proc Natl Acad Sci 2015; 112(51): E7073-82.
[http://dx.doi.org/10.1073/pnas.1521988112] [PMID: 26644565]
[122]
Gopal P, Sarathy JP, Yee M, et al. Pyrazinamide triggers degradation of its target aspartate decarboxylase. Nat Commun 2020; 11(1): 1661.
[http://dx.doi.org/10.1038/s41467-020-15516-1] [PMID: 32245967]
[123]
Mirnejad R, Asadi A, Khoshnood S, et al. Clofazimine: A useful antibiotic for drug-resistant tuberculosis. Biomed Pharmacother 2018; 105: 1353-9.
[http://dx.doi.org/10.1016/j.biopha.2018.06.023] [PMID: 30021373]
[124]
Manjunatha U, Boshoff HIM, Barry CE. The mechanism of action of PA-824. Commun Integr Biol 2009; 2(3): 215-8.
[http://dx.doi.org/10.4161/cib.2.3.7926] [PMID: 19641733]
[125]
Bushra E, Adem J. Mycobacterial metabolic pathways as drug targets: A review. Int J Microbiol Res 2016; 7(3): 74-87.
[126]
Gahoi S, Mandal RS, Ivanisenko N, et al. Computational screening for new inhibitors of M. tuberculosis mycolyltransferases antigen 85 group of proteins as potential drug targets. J Biomol Struct Dyn 2013; 31(1): 30-43.
[http://dx.doi.org/10.1080/07391102.2012.691343] [PMID: 22804492]
[127]
Ejalonibu MA, Elrashedy AA, Lawal MM, Kumalo HM, Mhlongo NN. Probing the dual inhibitory mechanisms of novel thiophenecarboxamide derivatives against Mycobacterium tuberculosis PyrG and PanK: An insight from biomolecular modeling study. J Biomol Struct Dyn 2022; 40(7): 2978-90.
[http://dx.doi.org/10.1080/07391102.2020.1844055] [PMID: 33155869]
[128]
Agre N, Khambete M, Maitra A, et al. Exploration of 5‐(5‐nitrothiophen‐2‐yl)‐4,5‐dihydro‐1H‐pyrazoles as selective, multitargeted antimycobacterial agents. Chem Biol Drug Des 2020; 95(1): 192-9.
[http://dx.doi.org/10.1111/cbdd.13624] [PMID: 31560814]
[129]
Banerjee DR, Biswas R, Das AK, Basak A. Design, synthesis and characterization of dual inhibitors against new targets FabG4 and HtdX of Mycobacterium tuberculosis. Eur J Med Chem 2015; 100: 223-34.
[http://dx.doi.org/10.1016/j.ejmech.2015.06.007] [PMID: 26092447]
[130]
Nguyen PC, Delorme V, Bénarouche A, et al. Oxadiazolone derivatives, new promising multi-target inhibitors against M. tuberculosis. Bioorg Chem 2018; 81: 414-24.
[http://dx.doi.org/10.1016/j.bioorg.2018.08.025] [PMID: 30212765]
[131]
Cheng YS, Sacchettini JC. Structural Insights into Mycobacterium tuberculosis Rv2671 protein as a dihydrofolate reductase functional analogue contributing to para -aminosalicylic acid resistance. Biochemistry 2016; 55(7): 1107-19.
[http://dx.doi.org/10.1021/acs.biochem.5b00993] [PMID: 26848874]
[132]
Hajian B, Scocchera E, Shoen C, et al. Drugging the folate pathway in mycobacterium tuberculosis: The role of multi-targeting agents. Cell Chem Biol 2019; 26(6): 781-791.e6.
[http://dx.doi.org/10.1016/j.chembiol.2019.02.013] [PMID: 30930162]
[133]
Zheng J, Rubin EJ, Bifani P, et al. para-Aminosalicylic acid is a prodrug targeting dihydrofolate reductase in Mycobacterium tuberculosis. J Biol Chem 2013; 288(32): 23447-56.
[http://dx.doi.org/10.1074/jbc.M113.475798] [PMID: 23779105]
[134]
Washburn A, Abdeen S, Ovechkina Y, et al. Dual-targeting Gro-EL/ES chaperonin and protein tyrosine phosphatase B (PtpB) inhibitors: A polypharmacology strategy for treating Mycobacterium tuberculosis infections. Bioorg Med Chem Lett 2019; 29(13): 1665-72.
[http://dx.doi.org/10.1016/j.bmcl.2019.04.034] [PMID: 31047750]
[135]
Kovalenko OP, Volynets GP, Rybak MY, et al. Dual-target inhibitors of mycobacterial aminoacyl-tRNA synthetases among N -benzylidene- N ′-thiazol-2-yl-hydrazines. Med Chem Comm 2019; 10(12): 2161-9.
[http://dx.doi.org/10.1039/C9MD00347A] [PMID: 32206244]
[136]
Volynets GP, Starosyla SA, Rybak MY, et al. Dual-targeted hit identification using pharmacophore screening. J Comput Aided Mol Des 2019; 33(11): 955-64.
[http://dx.doi.org/10.1007/s10822-019-00245-5] [PMID: 31691918]
[137]
Kumari M, Subbarao N. Identification of novel multitarget antitubercular inhibitors against mycobacterial peptidoglycan biosynthetic mur enzymes by structure-based virtual screening. J Biomol Struct Dyn 2021; 1-12.
[http://dx.doi.org/10.1080/07391102.2021.1908913] [PMID: 33826470]
[138]
Kaur P, Potluri V, Ahuja VK, et al. A multi-targeting pre-clinical candidate against drug-resistant tuberculosis. Tuberculosis 2021; 129: 102104.
[http://dx.doi.org/10.1016/j.tube.2021.102104] [PMID: 34214859]
[139]
Passi A, Rajput NK, Wild DJ, Bhardwaj A, Rep TB. RepTB: A gene ontology based drug repurposing approach for tuberculosis. J Cheminform 2018; 10(1): 24.
[http://dx.doi.org/10.1186/s13321-018-0276-9] [PMID: 29785561]
[140]
Haupt VJ, Daminelli S, Schroeder M. Drug promiscuity in PDB: Protein binding site similarity is key. PLoS One 2013; 8(6): e65894.
[http://dx.doi.org/10.1371/journal.pone.0065894] [PMID: 23805191]
[141]
Hu Y, Gupta-Ostermann D, Bajorath J. Exploring compound promiscuity patterns and multi-target activity spaces. Comput Struct Biotechnol J 2014; 9(13): e201401003.
[http://dx.doi.org/10.5936/csbj.201401003] [PMID: 24688751]
[142]
Kinnings SL, Xie L, Fung KH, Jackson RM, Xie L, Bourne PE. The Mycobacterium tuberculosis drugome and its polypharmacological implications. PLOS Comput Biol 2010; 6(11): e1000976.
[http://dx.doi.org/10.1371/journal.pcbi.1000976] [PMID: 21079673]
[143]
Anand P, Chandra N. Characterizing the pocketome of Mycobacterium tuberculosis and application in rationalizing polypharmacological target selection. Sci Rep 2014; 4(1): 6356.
[http://dx.doi.org/10.1038/srep06356] [PMID: 25220818]
[144]
Weinstein EA, Yano T, Li LS, et al. Inhibitors of type II NADH: Menaquinone oxidoreductase represent a class of antitubercular drugs. Proc Natl Acad Sci 2005; 102(12): 4548-53.
[http://dx.doi.org/10.1073/pnas.0500469102] [PMID: 15767566]
[145]
Maitra A, Bates S, Kolvekar T, Devarajan PV, Guzman JD, Bhakta S. Repurposing-a ray of hope in tackling extensively drug resistance in tuberculosis. Int J Infect Dis 2015; 32: 50-5.
[http://dx.doi.org/10.1016/j.ijid.2014.12.031] [PMID: 25809756]
[146]
Song L, Wu X. Development of efflux pump inhibitors in antituberculosis therapy. Int J Antimicrob Agents 2016; 47(6): 421-9.
[http://dx.doi.org/10.1016/j.ijantimicag.2016.04.007] [PMID: 27211826]
[147]
Kinnings SL, Liu N, Buchmeier N, Tonge PJ, Xie L, Bourne PE. Drug discovery using chemical systems biology: Repositioning the safe medicine Comtan to treat multi-drug and extensively drug resistant tuberculosis. PLOS Comput Biol 2009; 5(7): e1000423.
[http://dx.doi.org/10.1371/journal.pcbi.1000423] [PMID: 19578428]
[148]
Rybniker J, Vocat A, Sala C, et al. Lansoprazole is an antituberculous prodrug targeting cytochrome bc1. Nat Commun 2015; 6(1): 7659.
[http://dx.doi.org/10.1038/ncomms8659] [PMID: 26158909]
[149]
Rendon A, Tiberi S, Scardigli A, et al. Classification of drugs to treat multidrug-resistant tuberculosis (MDR-TB): evidence and perspectives. J Thorac Dis 2016; 8(10): 2666-71.
[http://dx.doi.org/10.21037/jtd.2016.10.14] [PMID: 27867538]
[150]
Quan D, Nagalingam G, Payne R, Triccas JA. New tuberculosis drug leads from naturally occurring compounds. Int J Infect Dis 2017; 56: 212-20.
[http://dx.doi.org/10.1016/j.ijid.2016.12.024] [PMID: 28062229]
[151]
Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol Adv 2015; 33(8): 1582-614.
[http://dx.doi.org/10.1016/j.biotechadv.2015.08.001] [PMID: 26281720]
[152]
Cazzaniga G, Mori M, Chiarelli LR, Gelain A, Meneghetti F, Villa S. Natural products against key Mycobacterium tuberculosis enzymatic targets: Emerging opportunities for drug discovery. Eur J Med Chem 2021; 224: 113732.
[http://dx.doi.org/10.1016/j.ejmech.2021.113732] [PMID: 34399099]
[153]
Nguta JM, Appiah-Opong R, Nyarko A K, Yeboah-Manu D, Addo P. G. Current perspectives in drug discovery against tuberculosis from natural products. Int J Mycobacteriol 2015; 4(3): 165-83.
[http://dx.doi.org/10.1016/j.ijmyco.2015.05.004]
[154]
Gupta VK, Kumar MM, Bisht D, Kaushik A. Plants in our combating strategies against Mycobacterium tuberculosis: Progress made and obstacles met. Pharm Biol 2017; 55(1): 1536-44.
[http://dx.doi.org/10.1080/13880209.2017.1309440] [PMID: 28385088]
[155]
Han J, Liu X, Zhang L, Quinn RJ, Feng Y. Anti-mycobacterial natural products and mechanisms of action. Nat Prod Rep 2022; 39(1): 77-89.
[http://dx.doi.org/10.1039/D1NP00011J] [PMID: 34226909]
[156]
Kumar S, Sahu P, Jena L. An In silico approach to identify potential inhibitors against multiple drug targets of Mycobacterium tuberculosis. Int J Mycobacteriol 2019; 8(3): 252-61.
[http://dx.doi.org/10.4103/ijmy.ijmy_109_19] [PMID: 31512601]
[157]
Kumari M, Singh R, Subbarao N. Exploring the interaction mechanism between potential inhibitor and multi-target mur enzymes of mycobacterium tuberculosis using molecular docking, molecular dynamics simulation, principal component analysis, free energy landscape, dynamic cross-correlation matrices, vector movements, and binding free energy calculation. J Biomol Struct Dyn 2021; 1-30.
[http://dx.doi.org/10.1080/07391102.2021.1989040] [PMID: 34662260]
[158]
Kumari M, Waseem M, Subbarao N. Discovery of multi-target mur enzymes inhibitors with anti-mycobacterial activity through a Scaffold approach. J Biomol Struct Dyn 2022; 1-22.
[http://dx.doi.org/10.1080/07391102.2022.2040593] [PMID: 35174764]
[159]
Ali MA, Farah MA, Lee J, Al-Anazi KM, Al-Hemaid FMA. Molecular insights into the interaction of ursolic acid and cucurbitacin from colocynth with therapeutic targets of Mycobacterium tuberculosis. Lett Drug Des Discov 2020; 17(10): 1309-18.
[http://dx.doi.org/10.2174/1570180817999200514102750]
[160]
Kumar M, Singh SK, Singh PP, et al. Potential anti-mycobacterium tuberculosis activity of plant secondary metabolites: Insight with molecular docking interactions. Antioxidants 2021; 10(12): 1990.
[http://dx.doi.org/10.3390/antiox10121990] [PMID: 34943093]
[161]
Antunes SS, Won-Held Rabelo V, Romeiro NC. Natural products from Brazilian biodiversity identified as potential inhibitors of PknA and PknB of M. tuberculosis using molecular modeling tools. Comput Biol Med 2021; 136: 104694.
[http://dx.doi.org/10.1016/j.compbiomed.2021.104694] [PMID: 34365277]
[162]
Abdulhamid A, Awad TA, Ahmed AE, Koua FHM, Ismail AM. Acetyleugenol from Acacia nilotica (L.) exhibits a strong antibacterial activity and its phenyl and indole analogues show a promising anti-TB potential targeting PknE/B protein kinases. Microbiol Res 2021; 12(1): 1-15.
[http://dx.doi.org/10.3390/microbiolres12010001]
[163]
Miryala SK, Basu S, Naha A, et al. Identification of bioactive natural compounds as efficient inhibitors against Mycobacterium tuberculosis protein-targets: A molecular docking and molecular dynamics simulation study. J Mol Liq 2021; 341: 117340.
[http://dx.doi.org/10.1016/j.molliq.2021.117340]
[164]
Ali MT, Blicharska N, Shilpi JA, Seidel V. Investigation of the anti-TB potential of selected propolis constituents using a molecular docking approach. Sci Rep 2018; 8(1): 12238.
[http://dx.doi.org/10.1038/s41598-018-30209-y] [PMID: 30116003]
[165]
Wang G, Dong W, Lu H, et al. Enniatin A1, a natural compound with bactericidal activity against mycobacterium tuberculosis in vitro. Molecules 2019; 25(1): 38.
[http://dx.doi.org/10.3390/molecules25010038]
[166]
Romano JD, Tatonetti NP. Informatics and computational methods in natural product drug discovery: A review and perspectives. Front Genet 2019; 10: 368.
[http://dx.doi.org/10.3389/fgene.2019.00368] [PMID: 31114606]
[167]
Macalino SJY, Billones JB, Organo VG, Carrillo MCO. In silico strategies in tuberculosis drug discovery. Molecules 2020; 25(3): 665.
[http://dx.doi.org/10.3390/molecules25030665] [PMID: 32033144]
[168]
Pushpakom S, Iorio F, Eyers PA, et al. Drug repurposing: Progress, challenges and recommendations. Nat Rev Drug Discov 2019; 18(1): 41-58.
[http://dx.doi.org/10.1038/nrd.2018.168] [PMID: 30310233]
[169]
Anighoro A, Bajorath J, Rastelli G. Polypharmacology: Challenges and opportunities in drug discovery. J Med Chem 2014; 57(19): 7874-87.
[http://dx.doi.org/10.1021/jm5006463] [PMID: 24946140]
[170]
Silva DR, Dalcolmo M, Tiberi S, et al. New and repurposed drugs to treat multidrug- and extensively drug-resistant tuberculosis. J Bras Pneumol 2018; 44(2): 153-60.
[http://dx.doi.org/10.1590/s1806-37562017000000436] [PMID: 29791557]
[171]
Fatima S, Bhaskar A, Dwivedi VP. Repurposing immunomodulatory drugs to combat tuberculosis. Front Immunol 2021; 12: 645485.
[http://dx.doi.org/10.3389/fimmu.2021.645485] [PMID: 33927718]
[172]
Mahmoud DB, Shitu Z, Mostafa A. Drug repurposing of nitazoxanide: Can it be an effective therapy for COVID-19? J Genet Eng Biotechnol 2020; 18(1): 35.
[http://dx.doi.org/10.1186/s43141-020-00055-5] [PMID: 32725286]
[173]
An Q, Li C, Chen Y, Deng Y, Yang T, Luo Y. Repurposed drug candidates for antituberculosis therapy. Eur J Med Chem 2020; 192: 112175.
[http://dx.doi.org/10.1016/j.ejmech.2020.112175] [PMID: 32126450]
[174]
Cardoso NC, Oosthuizen CB, Peton N, Singh V. Drug repurposing for tuberculosis. In: Saxena SK, Ed. Drug Repurposing – Molecular Aspects and Therapeutic Applications. London: Intech Open 2021.
[http://dx.doi.org/10.5772/intechopen.101393]
[175]
Sharma D, Dhuriya YK, Deo N, Bisht D. Repurposing and revival of the drugs: A new approach to combat the drug resistant tuberculosis. Front Microbiol 2017; 8: 2452.
[http://dx.doi.org/10.3389/fmicb.2017.02452] [PMID: 29321768]
[176]
Bose P, Harit AK, Das R, Sau S, Iyer AK, Kashaw SK. Tuberculosis: Current scenario, drug targets, and future prospects. Med Chem Res 2021; 30(4): 807-33.
[http://dx.doi.org/10.1007/s00044-020-02691-5]
[177]
Maitra A, Bates S, Shaik M, et al. Repurposing drugs for treatment of tuberculosis: a role for non-steroidal anti-inflammatory drugs. Br Med Bull 2016; 118(1): 138-48.
[http://dx.doi.org/10.1093/bmb/ldw019] [PMID: 27151954]
[178]
Lee C, Bhakta S. The prospect of repurposing immunomodulatory drugs for adjunctive chemotherapy against tuberculosis: A critical review. Antibiotics 2021; 10(1): 91.
[http://dx.doi.org/10.3390/antibiotics10010091] [PMID: 33477812]
[179]
Akinpelu O I, Lawal M M, Kumalo H M, Mhlongo N N. Drug repurposing: Fusidic acid as a potential inhibitor of M. tuberculosis FtsZ polymerization – Insight from DFT calculations, molecular docking and molecular dynamics simulations. Tuberculosis 2020; 121: 101920.
[http://dx.doi.org/10.1016/j.tube.2020.101920]
[180]
Pushkaran AC, Vinod V, Vanuopadath M, et al. Combination of repurposed drug diosmin with amoxicillin-clavulanic acid causes synergistic inhibition of mycobacterial growth. Sci Rep 2019; 9(1): 6800.
[http://dx.doi.org/10.1038/s41598-019-43201-x] [PMID: 31043655]
[181]
Ezquerra-Aznárez JM, Degiacomi G, Gašparovič H, et al. The veterinary anti-parasitic selamectin is a novel inhibitor of the Mycobacterium tuberculosis DprE1 Enzyme. Int J Mol Sci 2022; 23(2): 771.
[http://dx.doi.org/10.3390/ijms23020771] [PMID: 35054958]
[182]
Umapathy D, Soundhararajan R, Srinivasan H. Repurposing of FDA-Approved Drugs against Mycobacterium tuberculosis target MMA4 and CmaA2. Biointerface Res Appl Chem 2021; 11(6): 14688-96.
[http://dx.doi.org/10.33263/BRIAC116.1468814696]
[183]
Madugula SS, Nagamani S, Jamir E, Priyadarsinee L, Sastry GN. Drug repositioning for anti-tuberculosis drugs: An in silico polypharmacology approach. Mol Divers 2022; 26(3): 1675-95.
[http://dx.doi.org/10.1007/s11030-021-10296-2] [PMID: 34468898]
[184]
Battah B, Chemi G, Butini S, et al. A repurposing approach for uncovering the anti-tubercular activity of fda-approved drugs with potential multi-targeting profiles. Molecules 2019; 24(23): 4373.
[http://dx.doi.org/10.3390/molecules24234373] [PMID: 31795400]
[185]
Rani J, Silla Y, Borah K, Ramachandran S, Bajpai U. Repurposing of FDA-approved drugs to target MurB and MurE enzymes in Mycobacterium tuberculosis. J Biomol Struct Dyn 2020; 38(9): 2521-32.
[http://dx.doi.org/10.1080/07391102.2019.1637280] [PMID: 31244382]
[186]
Shinde Y, Ahmad I, Surana S, Patel H. The Mur Enzymes Chink in the Armour of Mycobacterium tuberculosis cell wall. Eur J Med Chem 2021; 222: 113568.
[http://dx.doi.org/10.1016/j.ejmech.2021.113568] [PMID: 34118719]
[187]
Brindha S, Vincent S, Velmurugan D, Ananthakrishnan D, Sundaramurthi JC, Gnanadoss JJ. Bioinformatics approach to prioritize known drugs towards repurposing for tuberculosis. Med Hypotheses 2017; 103: 39-45.
[http://dx.doi.org/10.1016/j.mehy.2017.04.005] [PMID: 28571806]
[188]
Ab Ghani NS, Ramlan EI, Firdaus-Raih M. Drug ReposER: A web server for predicting similar amino acid arrangements to known drug binding interfaces for potential drug repositioning. Nucleic Acids Res 2019; 47(W1): W350-6.
[http://dx.doi.org/10.1093/nar/gkz391] [PMID: 31106379]
[189]
Kleandrova VV, Scotti MT, Speck-Planche A. Computational drug repurposing for antituberculosis therapy: Discovery of multistrain inhibitors. Antibiotics 2021; 10(8): 1005.
[http://dx.doi.org/10.3390/antibiotics10081005] [PMID: 34439055]
[190]
Tiberi S, du Plessis N, Walzl G, et al. Tuberculosis: Progress and advances in development of new drugs, treatment regimens, and host-directed therapies. Lancet Infect Dis 2018; 18(7): e183-98.
[http://dx.doi.org/10.1016/S1473-3099(18)30110-5] [PMID: 29580819]
[191]
Young C, Walzl G, Du Plessis N. Therapeutic host-directed strategies to improve outcome in tuberculosis. Mucosal Immunol 2020; 13(2): 190-204.
[http://dx.doi.org/10.1038/s41385-019-0226-5] [PMID: 31772320]
[192]
Kiran D, Podell BK, Chambers M, Basaraba RJ. Host-directed therapy targeting the Mycobacterium tuberculosis granuloma: A review. Semin Immunopathol 2016; 38(2): 167-83.
[http://dx.doi.org/10.1007/s00281-015-0537-x] [PMID: 26510950]
[193]
Paik S, Kim JK, Chung C, Jo EK. Autophagy: A new strategy for host-directed therapy of tuberculosis. Virulence 2019; 10(1): 448-59.
[http://dx.doi.org/10.1080/21505594.2018.1536598] [PMID: 30322337]
[194]
Krug S, Parveen S, Bishai WR. Host-directed therapies: Modulating inflammation to treat tuberculosis. Front Immunol 2021; 12: 660916.
[http://dx.doi.org/10.3389/fimmu.2021.660916] [PMID: 33953722]
[195]
Guler R, Brombacher F. Host-directed drug therapy for tuberculosis. Nat Chem Biol 2015; 11(10): 748-51.
[http://dx.doi.org/10.1038/nchembio.1917] [PMID: 26379013]
[196]
Wetzel C, Lonneman M, Wu C. Polypharmacological drug actions of recently FDA approved antibiotics. Eur J Med Chem 2021; 209: 112931.
[http://dx.doi.org/10.1016/j.ejmech.2020.112931] [PMID: 33127170]
[197]
Wang H, Wang M, Xu X, et al. Multi-target mode of action of silver against Staphylococcus aureus endows it with capability to combat antibiotic resistance. Nat Commun 2021; 12(1): 3331.
[http://dx.doi.org/10.1038/s41467-021-23659-y] [PMID: 34099682]
[198]
Braga SS. Multi-target drugs active against leishmaniasis: A paradigm of drug repurposing. Eur J Med Chem 2019; 183: 111660.
[http://dx.doi.org/10.1016/j.ejmech.2019.111660] [PMID: 31514064]
[199]
Stampolaki M, Malwal SR, Alvarez-Cabrera N, et al. Synthesis and testing of analogs of the tuberculosis drug candidate sq109 against bacteria and protozoa: Identification of lead compounds against Mycobacterium abscessus and Malaria Parasites. ACS Infect Dis 2023; 9(2): 342-64.
[http://dx.doi.org/10.1021/acsinfecdis.2c00537] [PMID: 36706233]
[200]
Hoagland DT, Liu J, Lee RB, Lee RE. New agents for the treatment of drug-resistant Mycobacterium tuberculosis. Adv Drug Deliv Rev 2016; 102: 55-72.
[http://dx.doi.org/10.1016/j.addr.2016.04.026] [PMID: 27151308]
[201]
Bahuguna A, Rawat DS. An overview of new antitubercular drugs, drug candidates, and their targets. Med Res Rev 2020; 40(1): 263-92.
[http://dx.doi.org/10.1002/med.21602] [PMID: 31254295]
[202]
Conradie F, Diacon AH, Ngubane N, et al. Treatment of highly drug-resistant pulmonary tuberculosis. N Engl J Med 2020; 382(10): 893-902.
[http://dx.doi.org/10.1056/NEJMoa1901814] [PMID: 32130813]
[203]
FDA approves new treatment for highly drug-resistant forms of tuberculosis | TB Alliance. Available from: https://www.tballi-ance.org/news/fda-approves-new-treatment-highly-drug-resistant-forms-tuberculosis