Generic placeholder image

Infectious Disorders - Drug Targets

Author(s): Nongkhlaw Ridahunlang, Rohit Bisht and Nongkhlaw Rishanlang*

DOI: 10.2174/1871526522666221004152324

DownloadDownload PDF Flyer Cite As
Isoniazid Derivatives as Anti-Tubercular Agents: From Structural Design to Clinical Investigations

Article ID: e041022209552 Pages: 25

  • * (Excluding Mailing and Handling)

Abstract

Background: Tuberculosis (TB) is one of the fatal infectious diseases, making it one of the causes of death in the infectious mortality strata, and it is of prime concern globally. It is spread by a causative agent called Mycobacterium tuberculosis (Mtb) which gets ingressed within the host cells. The current clinical interventions have been associated with various limitations, such as a long treatment regimen (6 months), low lipophilicity of drugs to penetrate the bacterial cell, associated side effects and emerging incidence of multiple drug-resistant strains. Despite these limitations, Isoniazid (INH), a first-line agent, remains a drug of choice to date due to its effectiveness. However, INH is associated with poor penetration into the bacteria cell wall and ultimately leads to the low therapeutic distribution of drugs into the lungs.

Methods: Studies have shown that the structural modifications of INH by introducing more lipophilic moiety could lead to its better penetration into the bacterial cell wall resulting in better anti-TB activities.

Results: This review updates various studies conducted on INH derivatives as anti-tubercular (Anti-TB) agents, including in silico and preclinical investigations. In addition, updates on clinical investigations of novel anti-TB molecules have also been highlighted.

Conclusion: The article focuses on the structural modification of various INH derivatives reported, including the in vitro studies and molecular modelling preclinical and clinical investigations of various INH derivatives.

Keywords: Anti-TB agents, Anti-tubercular activity, Isoniazid, Isoniazid derivatives (INH), Multi Drug Resistance, Mycobacterium Tuberculosis (Mtb), Toxicity

Graphical Abstract

[1]
United Nations News, global perspective human stories: 1.4 million with tuberculosis, lost out on treatment during first year of COVID-19. United Nation News. Available from: https://news.Un.org/en/story/2021/03/
[2]
Eldehna W, Fares M, Abdel-Aziz M, Abdel-Aziz H. Design, synthesis and antitubercular activity of certain nicotinic Acid hydrazides. Molecules 2015; 20(5): 8800-15.
[http://dx.doi.org/10.3390/molecules20058800] [PMID: 25988611]
[3]
Gordon SV, Parish T. Microbe profile: Mycobacterium tuberculosis: Humanity’s deadly microbial foe. Microbiology (Reading) 2018; 164(4): 437-9.
[http://dx.doi.org/10.1099/mic.0.000601] [PMID: 29465344]
[4]
Ryan KJ, Ray CG. Medical microbiology. (4th ed.), Newyork: Mc Graw Hill 2004.
[5]
Chan ED, Iseman MD. Current medical treatment for tuberculosis. BMJ 2002; 325(7375): 1282-6.
[http://dx.doi.org/10.1136/bmj.325.7375.1282] [PMID: 12458250]
[6]
Telzak EE, Sepkowitz K, Alpert P, et al. Multidrug-resistant tuberculosis in patients without HIV infection. N Engl J Med 1995; 333(14): 907-12.
[http://dx.doi.org/10.1056/NEJM199510053331404] [PMID: 7666876]
[7]
Sia IG, Wieland ML. Current concepts in the management of tuberculosis. Mayo Clin Proc 2011; 86(4): 348-61.
[http://dx.doi.org/10.4065/mcp.2010.0820] [PMID: 21454737]
[8]
Mandell GL. Antimicrobial agents: Drugs used in the chemotherapy of tuberculosis and leprosy The pharmacological basis of therapeutics. (3rd ed.). USA: Goodman and Gilman's 1990; pp. 1013-21.
[9]
Deretic V, Pagán-Ramos E, Zhang Y, Dhandayuthapani S. via LE. The extreme sensitivity of Mycobacterium tuberculosis to the front-line antituberculosis drug isoniazid. Nat Biotechnol 1996; 14(11): 1557-61.
[http://dx.doi.org/10.1038/nbt1196-1557] [PMID: 9634820]
[10]
Blair IA, Mansilla Tinoco R, Brodie MJ, et al. Plasma hydrazine concentrations in man after isoniazid and hydralazine administration. Hum Toxicol 1985; 4(2): 195-202.
[http://dx.doi.org/10.1177/096032718500400210] [PMID: 4007883]
[11]
Zhang Y, Heym B, Allen B, Young D, Cole S. The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature 1992; 358(6387): 591-3.
[http://dx.doi.org/10.1038/358591a0] [PMID: 1501713]
[12]
Suarez J, Ranguelova K, Jarzecki AA, et al. An oxyferrous heme/protein-based radical intermediate is catalytically competent in the catalase reaction of Mycobacterium tuberculosis catalase-peroxidase (KatG). J Biol Chem 2009; 284(11): 7017-29.
[http://dx.doi.org/10.1074/jbc.M808106200] [PMID: 19139099]
[13]
Ghiladi RA, Medzihradszky KF, Rusnak FM, Ortiz de Montellano PR. Correlation between isoniazid resistance and superoxide reactivity in Mycobacterium tuberculosis KatG. J Am Chem Soc 2005; 127(38): 13428-42.
[http://dx.doi.org/10.1021/ja054366t] [PMID: 16173777]
[14]
Zhao X, Yu H, Yu S, Wang F, Sacchettini JC, Magliozzo RS. Hydrogen peroxide-mediated isoniazid activation catalyzed by Mycobacterium tuberculosis catalase-peroxidase (KatG) and its S315T mutant. Biochemistry 2006; 45(13): 4131-40.
[http://dx.doi.org/10.1021/bi051967o] [PMID: 16566587]
[15]
Wengenack NL, Rusnak F. Evidence for isoniazid-dependent free radical generation catalyzed by Mycobacterium tuberculosis KatG and the isoniazid-resistant mutant KatG(S315T). Biochemistry 2001; 40(30): 8990-6.
[http://dx.doi.org/10.1021/bi002614m] [PMID: 11467961]
[16]
Winder FG, Denneny JM. Metal-catalysed auto-oxidation of isoniazid. Biochem J 1959; 73(3): 500-7.
[http://dx.doi.org/10.1042/bj0730500] [PMID: 13845183]
[17]
Zinner K, Vidigal CCC, Durán N, Cilento G. Oxidation of isonicotinic acid hydrazide by the peroxidase system. Arch Biochem Biophys 1977; 180(2): 452-8.
[http://dx.doi.org/10.1016/0003-9861(77)90059-5] [PMID: 879795]
[18]
Timmins GS, Master S, Rusnak F, Deretic V. Nitric oxide generated from isoniazid activation by KatG: Source of nitric oxide and activity against Mycobacterium tuberculosis. Antimicrob Agents Chemother 2004; 48(8): 3006-9.
[http://dx.doi.org/10.1128/AAC.48.8.3006-3009.2004] [PMID: 15273113]
[19]
Marrakchi H, Lanéelle G, Quémard A. InhA, a target of the antituberculous drug isoniazid, is involved in a mycobacterial fatty acid elongation system, FAS-II. Microbiology (Reading) 2000; 146(2): 289-96.
[http://dx.doi.org/10.1099/00221287-146-2-289] [PMID: 10708367]
[20]
Sandy J, Mushtaq A, Kawamura A, Sinclair J, Sim E, Noble M. The structure of arylamine N-acetyltransferase from Mycobacterium smegmatis-an enzyme which inactivates the anti-tubercular drug, isoniazid. J Mol Biol 2002; 318(4): 1071-83.
[http://dx.doi.org/10.1016/S0022-2836(02)00141-9] [PMID: 12054803]
[21]
Sriram D, Yogeeswari P, Madhu K. Synthesis and in vitro and in vivo antimycobacterial activity of isonicotinoyl hydrazones. Bioorg Med Chem Lett 2005; 15(20): 4502-5.
[http://dx.doi.org/10.1016/j.bmcl.2005.07.011] [PMID: 16115763]
[22]
Shaharyar M, Siddiqui AA, Ali MA, Sriram D, Yogeeswari P. Synthesis and in vitro antimycobacterial activity of N1-nicotinoyl-3-(4′-hydroxy-3′-methyl phenyl)-5-[(sub)phenyl]-2-pyrazolines. Bioorg Med Chem Lett 2006; 16(15): 3947-9.
[http://dx.doi.org/10.1016/j.bmcl.2006.05.024] [PMID: 16725324]
[23]
Fox HH. The chemical approach to the control of tuberculosis. Science 1952; 116(3006): 129-34.
[http://dx.doi.org/10.1126/science.116.3006.129] [PMID: 14950210]
[24]
ER L The Chemistry and Chemotherapy of Tuberculosis. (3rd ed.), Baltimore: Williams & Wilkins 1958.
[25]
Vilchèze C, Jacobs WR Jr. The mechanism of isoniazid killing: Clarity through the scope of genetics. Annu Rev Microbiol 2007; 61(1): 35-50.
[http://dx.doi.org/10.1146/annurev.micro.61.111606.122346] [PMID: 18035606]
[26]
Sharma S, Sharma PK, Kumar N, Dudhe R. A review on various heterocyclic moieties and their antitubercular activity. Biomed Pharmacother 2011; 65(4): 244-51.
[http://dx.doi.org/10.1016/j.biopha.2011.04.005] [PMID: 21715130]
[27]
Kini S, Gandhi AM. Novel 2-pyrazoline derivatives as potential antibacterial and antifungal agents. Indian J Pharm Sci 2008; 70(1): 105-8.
[http://dx.doi.org/10.4103/0250-474X.40344] [PMID: 20390093]
[28]
Sharshira EM, Hamada NMM. Synthesis and antimicrobial evaluation of some pyrazole derivatives. Molecules 2012; 17(5): 4962-71.
[http://dx.doi.org/10.3390/molecules17054962] [PMID: 22547318]
[29]
Bashir R, Ovais S, Yaseen S, et al. Synthesis of some new 1,3,5-trisubstituted pyrazolines bearing benzene sulfonamide as anticancer and anti-inflammatory agents. Bioorg Med Chem Lett 2011; 21(14): 4301-5.
[http://dx.doi.org/10.1016/j.bmcl.2011.05.061] [PMID: 21664130]
[30]
Özdemir Z, Kandilci HB. Gümüşel B, Çalış Ü Bilgin AA. Synthesis and studies on antidepressant and anticonvulsant activities of some 3-(2-furyl)-pyrazoline derivatives. Eur J Med Chem 2007; 42(3): 373-9.
[http://dx.doi.org/10.1016/j.ejmech.2006.09.006] [PMID: 17069933]
[31]
Abunada N, Hassaneen H, Kandile N, Miqdad O. Synthesis and biological activity of some new pyrazoline and pyrrolo[3,4-c]pyrazole-4,6-dione derivatives: Reaction of nitrilimines with some dipolarophiles. Molecules 2008; 13(4): 1011-24.
[http://dx.doi.org/10.3390/molecules13041011] [PMID: 18463603]
[32]
Shaaban MR, Mayhoub AS, Farag AM. Recent advances in the therapeutic applications of pyrazolines. Expert Opin Ther Pat 2012; 22(3): 253-91.
[http://dx.doi.org/10.1517/13543776.2012.667403] [PMID: 22397588]
[33]
Ali MA, Yar MS, Kumar M, Pandian GS. Synthesis and antitubercular activity of substituted novel pyrazoline derivatives. Nat Prod Res 2007; 21(7): 575-9.
[http://dx.doi.org/10.1080/14786410701369367] [PMID: 17613813]
[34]
Ahmad A, Husain A, Khan SA, Mujeeb M, Bhandari A. Synthesis, antimicrobial and antitubercular activities of some novel pyrazoline derivatives. J Saudi Chem Soc 2016; 20(5): 577-84.
[http://dx.doi.org/10.1016/j.jscs.2014.12.004]
[35]
Manna K, Agrawal YK. Design, synthesis, and antitubercular evaluation of novel series of 3-benzofuran-5-aryl-1-pyrazolyl-pyridylmethanone and 3-benzofuran-5-aryl-1-pyrazolylcarbonyl-4-oxo-naphthyridin analogs. Eur J Med Chem 2010; 45(9): 3831-9.
[http://dx.doi.org/10.1016/j.ejmech.2010.05.035] [PMID: 20576327]
[36]
PopiołekŁ. Hydrazide-hydrazones as potential antimicrobial agents: Overview of the literature since 2010. Med Chem Res 2017; 26(2): 287-301.
[http://dx.doi.org/10.1007/s00044-016-1756-y] [PMID: 28163562]
[37]
Maccari R, Ottanà R, Monforte F, Vigorita MG. In vitro antimycobacterial activities of 2′-monosubstituted isonicotinohydrazides and their cyanoborane adducts. Antimicrob Agents Chemother 2002; 46(2): 294-9.
[http://dx.doi.org/10.1128/AAC.46.2.294-299.2002] [PMID: 11796333]
[38]
Maccari R, Ottanà R, Vigorita MG. In vitro advanced antimycobacterial screening of isoniazid-related hydrazones, hydrazides and cyanoboranes: Part 14. Bioorg Med Chem Lett 2005; 15(10): 2509-13.
[http://dx.doi.org/10.1016/j.bmcl.2005.03.065] [PMID: 15863306]
[39]
Vigorita MG, Basile M, Zappalà C, Gabbrielli G, Pizzimenti F. Halogenated isoniazid derivatives as possible antitubercular and antineoplastic agents. Note 1. Farmaco 1992; 47(6): 893-906.
[PMID: 1388607]
[40]
Vavříková E, Polanc S, Kočevar M, et al. New series of isoniazid hydrazones linked with electron-withdrawing substituents. Eur J Med Chem 2011; 46(12): 5902-9.
[http://dx.doi.org/10.1016/j.ejmech.2011.09.054] [PMID: 22018878]
[41]
Sriram D, Yogeeswari P, Madhu K. Synthesis and in vitro antitubercular activity of some 1-[(4-sub) phenyl]-3-(4-{1-[(pyridine-4-carbonyl) hydrazono] ethyl} phenyl) thiourea. Bioorg Med Chem Lett 2006; 16(4): 876-8.
[http://dx.doi.org/10.1016/j.bmcl.2005.11.004] [PMID: 16303302]
[42]
Swamy BN, Suma TK, Rao GV, Reddy GC. Synthesis of isonicotinoylhydrazones from anacardic acid and their in vitro activity against Mycobacterium smegmatis. Eur J Med Chem 2007; 42(3): 420-4.
[http://dx.doi.org/10.1016/j.ejmech.2006.09.009] [PMID: 17112641]
[43]
Bottari B, Maccari R, Monforte F, Ottanà R, Rotondo E, Vigorita MG. Isoniazid-related copper(II) and nickel(II) complexes with antimycobacterial in vitro activity. Part 9. Bioorg Med Chem Lett 2000; 10(7): 657-60.
[http://dx.doi.org/10.1016/S0960-894X(00)00058-5] [PMID: 10762047]
[44]
Bottari B, Maccari R, Monforte F, Ottanà R, Rotondo E, Vigorita MG. Antimycobacterial in vitro activity of cobalt(II) isonicotinoylhydrazone complexes. Part 10. Bioorg Med Chem Lett 2001; 11(3): 301-3.
[http://dx.doi.org/10.1016/S0960-894X(00)00648-X] [PMID: 11212096]
[45]
Lourenço MCS, Ferreira ML, de Souza MVN, Peralta MA, Vasconcelos TRA, Henriques MGMO. Synthesis and anti-mycobacterial activity of (E)-N′-(monosubstituted-benzylidene)] isonicotinohydrazide derivatives. Eur J Med Chem 2008; 43(6): 1344-7.
[http://dx.doi.org/10.1016/j.ejmech.2007.08.003] [PMID: 17923172]
[46]
Narang R, Narasimhan B, Sharma S, et al. Synthesis, antimycobacterial, antiviral, antimicrobial activities, and QSAR studies of nicotinic acid benzylidene hydrazide derivatives. Med Chem Res 2012; 21(8): 1557-76.
[http://dx.doi.org/10.1007/s00044-011-9664-7]
[47]
Mir F, Shafi S, Zaman MS, et al. Sulfur rich 2-mercaptobenzothiazole and 1,2,3-triazole conjugates as novel antitubercular agents. Eur J Med Chem 2014; 76: 274-83.
[http://dx.doi.org/10.1016/j.ejmech.2014.02.017] [PMID: 24589483]
[48]
Almeida da Silva PE, Ramos DF, Bonacorso HG, et al. Synthesis and in vitro antimycobacterial activity of 3-substituted 5-hydroxy-5-trifluoro[chloro]methyl-4,5-dihydro-1H-1-(isonicotinoyl) pyrazoles. Int J Antimicrob Agents 2008; 32(2): 139-44.
[http://dx.doi.org/10.1016/j.ijantimicag.2008.03.019] [PMID: 18571384]
[49]
Nayak N, Ramprasad J, Dalimba U. New INH–pyrazole analogs: Design, synthesis and evaluation of antitubercular and antibacterial activity. Bioorg Med Chem Lett 2015; 25(23): 5540-5.
[http://dx.doi.org/10.1016/j.bmcl.2015.10.057] [PMID: 26520663]
[50]
Bolakatti GS, Maddi VS, Mamledesai SN, Ronad PM, Palkar MB, Swamy S. Synthesis and evaluation of antiinflammatory and analgesic activities of a novel series of coumarin Mannich bases. Arzneimittelforschung 2008; 58(10): 515-20.
[PMID: 19025062]
[51]
Karthikeyan MS, Holla BS, Kumari NS. Synthesis and antimicrobial studies on novel chloro-fluorine containing hydroxy pyrazolines. Eur J Med Chem 2007; 42(1): 30-6.
[http://dx.doi.org/10.1016/j.ejmech.2006.07.011] [PMID: 17007964]
[52]
Aragade P, Maddi V, Khode S, et al. Synthesis and antibacterial activity of a new series of 3-[3-(substituted phenyl)-1-isonicotinoyl-1H-pyrazol-5-yl]-2H-chromen-2-one derivatives. Arch Pharm (Weinheim) 2009; 342(6): 361-6.
[http://dx.doi.org/10.1002/ardp.200800156] [PMID: 19475595]
[53]
Aragade P, Palkar M, Ronad P, Satyanarayana D. Coumarinyl pyrazole derivatives of INH: Promising antimycobacterial agents. Med Chem Res 2013; 22(5): 2279-83.
[http://dx.doi.org/10.1007/s00044-012-0222-8]
[54]
Genin MJ, Allwine DA, Anderson DJ, et al. Substituent effects on the antibacterial activity of nitrogen-carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis. J Med Chem 2000; 43(5): 953-70.
[http://dx.doi.org/10.1021/jm990373e] [PMID: 10715160]
[55]
Holla BS, Mahalinga M, Karthikeyan MS, Poojary B, Akberali PM, Kumari NS. Synthesis, characterization and antimicrobial activity of some substituted 1,2,3-triazoles. Eur J Med Chem 2005; 40(11): 1173-8.
[http://dx.doi.org/10.1016/j.ejmech.2005.02.013] [PMID: 15979767]
[56]
Zhang Q, Peng Y, Wang XI, Keenan SM, Arora S, Welsh WJ. Highly potent triazole-based tubulin polymerization inhibitors. J Med Chem 2007; 50(4): 749-54.
[http://dx.doi.org/10.1021/jm061142s] [PMID: 17249649]
[57]
Biagi G, Dell’Omodarme G, Ferretti M, et al. Studies on 1,2,3-triazole derivatives as in vitro inhibitors of prostaglandin synthesis. Farmaco 1990; 45(11): 1181-92.
[PMID: 2128450]
[58]
Kumar D. Beena, Khare G, et al. Synthesis of novel 1,2,3-triazole derivatives of isoniazid and their in vitro and in vivo antimycobacterial activity evaluation. In Vivo 2014; 81: 301-13.
[PMID: 24852277]
[59]
Joshi MC, Bisht GS, Rawat DS. Syntheses and antibacterial activity of phendioxy substituted cyclic enediynes. Bioorg Med Chem Lett 2007; 17(11): 3226-30.
[http://dx.doi.org/10.1016/j.bmcl.2007.03.007] [PMID: 17433674]
[60]
Atheaya H, Khan SI, Mamgain R, Rawat DS. Synthesis, thermal stability, antimalarial activity of symmetrically and asymmetrically substituted tetraoxanes. Bioorg Med Chem Lett 2008; 18(4): 1446-9.
[http://dx.doi.org/10.1016/j.bmcl.2007.12.069] [PMID: 18248990]
[61]
Beena Kumar N, Rohilla RK, Roy N, Rawat DS. Synthesis and antibacterial activity evaluation of metronidazole-triazole conjugates. Bioorg Med Chem Lett 2009; 19(5): 1396-8.
[http://dx.doi.org/10.1016/j.bmcl.2009.01.037] [PMID: 19195884]
[62]
Kumar N, Khan SI. Beena, Rajalakshmi G, Kumaradhas P, Rawat DS. Synthesis, antimalarial activity and cytotoxicity of substituted 3,6-diphenyl-[1,2,4,5]tetraoxanes. Bioorg Med Chem 2009; 17(15): 5632-8.
[http://dx.doi.org/10.1016/j.bmc.2009.06.020] [PMID: 19574054]
[63]
Manohar S, Khan SI, Rawat DS. Synthesis, antimalarial activity and cytotoxicity of 4-aminoquinoline-triazine conjugates. Bioorg Med Chem Lett 2010; 20(1): 322-5.
[http://dx.doi.org/10.1016/j.bmcl.2009.10.106] [PMID: 19910192]
[64]
Dias MVB, Vasconcelos IB, Prado AMX, et al. Crystallographic studies on the binding of isonicotinyl-NAD adduct to wild-type and isoniazid resistant 2-trans-enoyl-ACP (CoA) reductase from Mycobacterium tuberculosis. J Struct Biol 2007; 159(3): 369-80.
[http://dx.doi.org/10.1016/j.jsb.2007.04.009] [PMID: 17588773]
[65]
Hartkoorn RC, Sala C, Neres J, et al. Towards a new tuberculosis drug: Pyridomycin-nature’s isoniazid. EMBO Mol Med 2012; 4(10): 1032-42.
[http://dx.doi.org/10.1002/emmm.201201689] [PMID: 22987724]
[66]
Maestro. Schrödinger Release 2022-3: Maestro, Schrödinger, LLC, New York, NY, 2021.
[67]
Boechat N, Ferreira VF, Ferreira SB, et al. Novel 1,2,3-triazole derivatives for use against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain. J Med Chem 2011; 54(17): 5988-99.
[http://dx.doi.org/10.1021/jm2003624] [PMID: 21776985]
[68]
Phatak PS, Sathe BP, Dhumal ST, et al. Synthesis, antimicrobial evaluation, and docking studies of substituted acetylphenoxymethyl‐triazolyl‐N‐phenylacetamides. J Heterocycl Chem 2019; 56(7): 1928-38.
[http://dx.doi.org/10.1002/jhet.3568]
[69]
Mahesh B, Muluk PSP, Pawar SB, et al. Synthesis, antimicrobial, and antioxidant activities of new pyridyl‐and thiazolyl‐bearing carbohydrazides. J Chin Chem Soc (Taipei) 2019; 66(11): 1507-17.
[70]
Adinath D, Badar SMS, Mahesh B, et al. Synthesis of isoniazid-1,2,3-triazole conjugates: Antitubercular, antimicrobial evaluation and molecular docking study. J Heterocycl Chem 2020; 57(10): 3544-57.
[71]
Patil PS, Kasare SL, Haval NB, et al. Novel isoniazid embedded triazole derivatives: Synthesis, antitubercular and antimicrobial activity evaluation. Bioorg Med Chem Lett 2020; 30(19)127434
[http://dx.doi.org/10.1016/j.bmcl.2020.127434] [PMID: 32717369]
[72]
Rastogi N, Goh KS, Horgen L, Barrow WW. Synergistic activities of antituberculous drugs with cerulenin and trans-cinnamic acid against Mycobacterium tuberculosis. FEMS Immunol Med Microbiol 1998; 21(2): 149-57.
[http://dx.doi.org/10.1111/j.1574-695X.1998.tb01161.x] [PMID: 9685005]
[73]
Carvalho SA, da Silva EF, de Souza MVN, Lourenço MCS, Vicente FR. Synthesis and antimycobacterial evaluation of new trans-cinnamic acid hydrazide derivatives. Bioorg Med Chem Lett 2008; 18(2): 538-41.
[http://dx.doi.org/10.1016/j.bmcl.2007.11.091] [PMID: 18068364]
[74]
De P, Koumba Yoya G, Constant P, et al. Design, synthesis, and biological evaluation of new cinnamic derivatives as antituberculosis agents. J Med Chem 2011; 54(5): 1449-61.
[http://dx.doi.org/10.1021/jm101510d] [PMID: 21309577]
[75]
Byler KG, Wang C, Setzer WN. Quinoline alkaloids as intercalative topoisomerase inhibitors. J Mol Model 2009; 15(12): 1417-26.
[http://dx.doi.org/10.1007/s00894-009-0501-6] [PMID: 19424733]
[76]
Keri RS, Patil SA. Quinoline: A promising antitubercular target. Biomed Pharmacother 2014; 68(8): 1161-75.
[http://dx.doi.org/10.1016/j.biopha.2014.10.007] [PMID: 25458785]
[77]
Santivañez-Veliz M, Pérez-Silanes S, Torres E, Moreno-Viguri E. Design and synthesis of novel quinoxaline derivatives as potential candidates for treatment of multidrug-resistant and latent tuberculosis. Bioorg Med Chem Lett 2016; 26(9): 2188-93.
[http://dx.doi.org/10.1016/j.bmcl.2016.03.066] [PMID: 27025343]
[78]
Jaso A, Zarranz B, Aldana I, Monge A. Synthesis of new 2-acetyl and 2-benzoyl quinoxaline 1,4-di-N-oxide derivatives as anti-Mycobacterium tuberculosis agents. Eur J Med Chem 2003; 38(9): 791-800.
[http://dx.doi.org/10.1016/S0223-5234(03)00137-5] [PMID: 14561478]
[79]
Zarranz B, Jaso A, Aldana I, Monge A. Synthesis and antimycobacterial activity of new quinoxaline-2-carboxamide 1,4-di-N-Oxide derivatives. Bioorg Med Chem 2003; 11(10): 2149-56.
[http://dx.doi.org/10.1016/S0968-0896(03)00119-6] [PMID: 12713824]
[80]
Navarrete-Vázquez G, Molina-Salinas GM, Duarte-Fajardo ZV, et al. Synthesis and antimycobacterial activity of 4-(5-substituted-1,3,4-oxadiazol-2-yl)pyridines. Bioorg Med Chem 2007; 15(16): 5502-8.
[http://dx.doi.org/10.1016/j.bmc.2007.05.053] [PMID: 17562368]
[81]
Torres E, Moreno E, Ancizu S, et al. New 1,4-di-N-oxide-quinoxaline-2-ylmethylene isonicotinic acid hydrazide derivatives as anti-Mycobacterium tuberculosis agents. Bioorg Med Chem Lett 2011; 21(12): 3699-703.
[http://dx.doi.org/10.1016/j.bmcl.2011.04.072] [PMID: 21570839]
[82]
Aboul-Fadl T, Mohammed FAH, Hassan EAS. Synthesis, antitubercular activity and pharmacokinetic studies of some schiff bases derived from 1- alkylisatin and isonicotinic acid hydrazide (inh). Arch Pharm Res 2003; 26(10): 778-84.
[http://dx.doi.org/10.1007/BF02980020] [PMID: 14609123]
[83]
Hussein M, Aboul-Fadl T, Hussein A. Synthesis and antitubercular activity of some mannich bases derived from isatin isonicotinic acid hydrazone. Bull Pharm Sci 2005; 28(1): 131-6.
[http://dx.doi.org/10.21608/bfsa.2005.65240]
[84]
O’Brien R. Scientific blueprint for tuberculosis drug development (Global alliance for TB drug development). Tuberculosis (Edinb) 2001; 81(1): 1-52.
[85]
Lenaerts AJ, DeGroote MA, Orme IM. Preclinical testing of new drugs for tuberculosis: Current challenges. Trends Microbiol 2008; 16(2): 48-54.
[http://dx.doi.org/10.1016/j.tim.2007.12.002] [PMID: 18182291]
[86]
Guzman JD, Montes-Rincon X, Ribon W. Research and development of new drugs against tuberculosis.In: Tuberculosis-current issues in diagnosis and management. Rijeka: InTech 2013; pp. 331-58.
[87]
LL-3858 (Sudoterb), a potential candidate for the treatment of MDR tuberculosis. Available from: https://newdrugapprovals.org/ 2017/12/05/ll-3858-sudoterb/ (Accessed on: March 01, 2022).
[88]
Tiberi S, Vjecha MJ, Zumla A, Galvin J, Migliori GB, Zumla A. Accelerating development of new shorter TB treatment regimens in anticipation of a resurgence of multi-drug resistant TB due to the COVID-19 pandemic. Int J Infect Dis 2021; 113 (Suppl. 1): S96-9.
[http://dx.doi.org/10.1016/j.ijid.2021.02.067] [PMID: 33713815]
[89]
Martins F, Santos S, Ventura C, et al. Design, synthesis and biological evaluation of novel isoniazid derivatives with potent antitubercular activity. Eur J Med Chem 2014; 81: 119-38.
[http://dx.doi.org/10.1016/j.ejmech.2014.04.077] [PMID: 24836065]
[90]
Ventura C, Martins F. Application of quantitative structure-activity relationships to the modeling of antitubercular compounds. 1. The hydrazide family. J Med Chem 2008; 51(3): 612-24.
[http://dx.doi.org/10.1021/jm701048s] [PMID: 18176999]
[91]
Rychtarčíková Z, Krátký M, Gazvoda M, et al. N-substituted 2- isonicotinoylhydrazinecarboxamides-new antimycobacterial active molecules. Molecules 2014; 19(4): 3851-68.
[http://dx.doi.org/10.3390/molecules19043851] [PMID: 24686575]
[92]
Pavan FR, Maia PIS, Leite SRA, et al. Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones: Anti – Mycobacterium tuberculosis activity and cytotoxicity. Eur J Med Chem 2010; 45(5): 1898-905.
[http://dx.doi.org/10.1016/j.ejmech.2010.01.028] [PMID: 20163897]
[93]
Castelo-Branco FS, de Lima EC, Domingos JLO, et al. New hydrazides derivatives of isoniazid against Mycobacterium tuberculosis: Higher potency and lower hepatocytotoxicity. Eur J Med Chem 2018; 146: 529-40.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.071] [PMID: 29407978]
[94]
Sampiron EG, Costacurta GF, Baldin VP, et al. Hydrazone, benzohydrazones and isoniazid-acylhydrazones as potential antituberculosis agents. Future Microbiol 2019; 14(11): 981-94.
[http://dx.doi.org/10.2217/fmb-2019-0040] [PMID: 31382801]
[95]
Zarafu I, Matei L, Bleotu C, et al. Synthesis, characterization, and biologic activity of new acyl hydrazides and 1,3,4-oxadiazole derivatives. Molecules 2020; 25(14): 3308.
[http://dx.doi.org/10.3390/molecules25143308] [PMID: 32708236]
[96]
Dayakar C, Suman P, Rajkumar K, Yogeeswari P, Sriram D, Raju B. Synthesis and anti-mycobacterial activity of 1H-1, 2, 3-triazolyl isonicotinohydrazides. Indian J Chem 2016; (55B): 882-7.
[97]
Babu RR, Naresh K, Ravi A, Madhava Reddy B, Harinadha Babu V. Synthesis of novel isoniazid incorporated styryl quinazolinones as anti-tubercular agents against INH sensitive and MDR M. tuberculosis strains. Med Chem Res 2014; 23(10): 4414-9.
[http://dx.doi.org/10.1007/s00044-014-1020-2]
[98]
Elsayed ZM, Eldehna WM, Abdel-Aziz MM, et al. Development of novel isatin–nicotinohydrazide hybrids with potent activity against susceptible/resistant Mycobacterium tuberculosis and bronchitis causing-bacteria. J Enzyme Inhib Med Chem 2021; 36(1): 384-92.
[http://dx.doi.org/10.1080/14756366.2020.1868450] [PMID: 33406941]
[99]
US National Library of Medicine. An exploratory study of TMC207 in Japanese participants with pulmonary multi-drug resistant tuberculosis (MDR-TB). NCT02365623 2019. Available from: https://clinicaltrials.gov/ct2/show/NCT02365623 (Accessed on: March 01, 2022).
[100]
US National Library of Medicine. Evaluation of the safety, tolerability, PK of TBAJ-587 in healthy adults. NCT04890535 2021. Available from: https://clinicaltrials.gov/ct2/show/NCT04890535 (Accessed on: March 01, 2022).
[101]
US National Library of Medicine. Evaluate safety, tolerability, PK of TBAJ-876 in healthy adults. NCT04493671 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT04493671 (Accessed on: March 01, 2022).
[102]
US National Library of Medicine. A phase 2, multi-center, uncontrolled, open-label trial to evaluate safety, tolerability, and efficacy of orally administered OPC-67683. NCT02573350 2015. Available from: https://clinicaltrials.gov/ct2/show/NCT02573350 (Accessed on: March 01, 2022).
[103]
US National Library of Medicine. A study of the safety, tolerability, and absorption, metabolism, and excretion of PA-824 in healthy adult male subjects (CL-004). NCT03202693 2018. Available from: https://clinicaltrials.gov/ct2/show/NCT03202693 (Accessed on: March 01, 2022).
[104]
US National Library of Medicine. A phase 2 study to evaluate early bactericidal activity, safety, tolerability, and pharmacokinetics of multiple oral doses of telacebec (Q203). NCT03563599 2019. Available from: https://clinicaltrials.gov/ct2/show/NCT03563599 (Accessed on: March 01, 2022).
[105]
US National Library of Medicine. Phase 2a EBA trial of AZD5847 NCT01516203 2018. Available from: https://clinicaltrials.gov/ct2/show/NCT01516203 (Accessed on: March 01, 2022).
[106]
US National Library of Medicine. PNU-100480 in newly diagnosed, drug sensitive patients with pulmonary TB. 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT01225640 (Accessed on: March 01, 2022).
[107]
US National Library of Medicine. Study to evaluate safety, tolerability, and the PK profile of TBI-223 in healthy subjects. NCT04865536 2021. Available from: https://clinicaltrials.gov/ct2/show/NCT04865536 (Accessed on: March 01, 2022).
[108]
US National Library of Medicine. A phase II clinical study of LCB01-0371 to evaluate the EBA, safety and PK. NCT02836483 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT02836483 (Accessed on: March 01, 2022).
[109]
US National Library of Medicine. BTZ-043 - multiple ascending dose (MAD) to evaluate safety, tolerability and early bactericidal activity (EBA). NCT04044001 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT04044001 (Accessed on: March 01, 2022).
[110]
US National Library of Medicine. Study to evaluate the safety, tolerability and pharmacokinetics of PBTZ169 in multiple dosing. NCT03776500 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT03776500 (Accessed on: March 01, 2022).
[111]
US National Library of Medicine. Early Bactericidal Activity (EBA) of SQ109 in adult subjects with pulmonary TB (SQ109EBA). NCT01218217 2013. Available from: https://clinicaltrials.gov/ct2/show/NCT01218217 (Accessed on: March 01, 2022).
[112]
Clinical Trials.gov.in, US National Library of Medicine. Early Bactericidal Activity Safety Pulmonary Tuberculosis Pyrifazimine (TBI-166) NCT04670120 2021. Available from: https://clinicaltrials.gov/ct2/show/NCT04670120 (Accessed on: March 01, 2022).
[113]
US National Library of Medicine. Evaluation of early bactericidal activity in pulmonary tuberculosis with clofazimine (C)-TMC207 (J)-PA-824 (Pa)-Pyrazinamide (Z) (NC-003). NCT01691534 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT01691534 (Accessed on: March 01, 2022).