Synthesis, Molecular Docking, c-Met Inhibitions of 2,2,2-Trichloroethylidene- cyclohexane-1, 3-dione Derivatives Together with their Application as Target SARS-CoV-2 main Protease (Mpro) and as Potential anti-COVID-19

Page: [1437 - 1449] Pages: 13

  • * (Excluding Mailing and Handling)

Abstract

Background: The lack of anti-COVID-19 treatment to date warrants urgent research into potential therapeutic targets. Virtual drug screening techniques enable the identification of novel compounds that target the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Main Protease (Mpro).

Objective: The binding of the halogenated compounds to Mpro may inhibit the replication and transcription of SARS-CoV-2 and, ultimately, stop the viral life cycle. In times of dire need for anti- COVID-19 treatment, this study lays the groundwork for further experimental research to investigate these compounds' efficacy and potential medical uses to treat COVID-19.

Methods: New heterocyclic compounds were synthesized through the first reaction of cyclohexane- 1, 3-dione (1a) or dimedone (1b) with trichloroacetonitrile (2) to give the 2,2,2-trichloroethylidene) cyclohexane-1,3-dione derivatives 3a and 3b, respectively. The latter compounds underwent a series of heterocyclization reactions to produce biologically active compounds.

Results: Novel compounds, including fused thiophene, pyrimidine and pyran derivatives, were synthesized and tested against human RNA N7-MTase (hRNMT) and selected viral N7-MTases such as SARS-CoV nsp14 and Vaccinia D1-D12 complex to evaluate their specificity and their molecular modeling was also studied in the aim of producing anti-COVID-19 target molecules.

Conclusion: The results showed that compounds 10a, 10b, 10c, 10e, 10f, 10g and 10h showed high % inhibitions against SARs-Covnsp 14. Whereas compounds 5a, 7a, 8b, 10a, 10b, 10c and 10i showed high inhibitions against hRNMT. This study explored the binding affinity of twenty-two halogenated compounds to the SARS-CoV-2 MPro and discovered fifteen compounds with higher binding affinity than Nelfinavir, of which three showed remarkable results. c-Met kinase inhibitions of 10a, 10f, 10g and 10h showed that all compounds exhibited higher inhibitions than the reference Foretinib.

Keywords: Trichloroethylidene, SARS-CoV-2, Corona virus, Main protease, Mpro, Molecular Docking

Graphical Abstract

[1]
Abbasi, B.A.; Iqbal, J.; Kiran, F.; Ahmad, R.; Kanwal, S.; Munir, A.; Uddin, S.; Nasir, J.A.; Chalgham, W.; Mahmood, T. Green formulation and chemical characterizations of Rhamnella gilgitica aqueous leaves extract conjugated NiONPs and their multiple therapeutic properties. J. Mol. Struct., 2020, 1218, 128490.
[http://dx.doi.org/10.1016/j.molstruc.2020.128490]
[2]
Goldsmith, M.R.; Tornero-Velez, R.; Transue, T.R.; Little, S.B.; Rabinowitz, J.R.; Dary, C.C. Comparative in silico modeling of environmental and therapeutic classes of perfluorinated chemicals (PFCS): ADME properties, virtual receptor profiling and generalized PBPK models. Reprod. Toxicol., 2009, 27(3-4), 419-420.
[http://dx.doi.org/10.1016/j.reprotox.2008.11.065]
[3]
Schiavon, O.; Caliceti, P.; Ferruti, P.; Veronese, F.M. Therapeutic proteins: A comparison of chemical and biological properties of uricase conjugated to linear or branched poly(ethylene glycol) and poly(N-acryloylmorpholine). Farmaco, 2000, 55(4), 264-269.
[http://dx.doi.org/10.1016/S0014-827X(00)00031-8] [PMID: 10966157]
[4]
Liang, H.; Hu, B.; Chen, L.; Wang, S. Aorigele, Recognizing novel chemicals/drugs for anatomical therapeutic chemical classes with a heat diffusion algorithm. Biochim. Biophys. Acta Mol. Basis Dis., 2020, 1866(11), 165910.
[http://dx.doi.org/10.1016/j.bbadis.2020.165910]
[5]
Tosstorff, A.; Menzen, T.; Winter, G. Exploring chemical space for new substances to stabilize a therapeutic monoclonal antibody. J. Pharm. Sci., 2020, 109(1), 301-307.
[http://dx.doi.org/10.1016/j.xphs.2019.10.057] [PMID: 31697947]
[6]
Talebi, M.; Talebi, M.; Farkhondeh, T.; Samarghandian, S. Molecular mechanism-based therapeutic properties of honey. Biomed. Pharmacother., 2020, 130, 110590.
[http://dx.doi.org/10.1016/j.biopha.2020.110590] [PMID: 32768885]
[7]
Marican, A.; Forero-Doria, O.; Polo, E.; Gallego, J.; Durán-Lara, E.F. Data of preparation and evaluation of supramolecular hydrogel based on cellulose for sustained release of therapeutic substances with antimicrobial and wound healing properties. Data Brief, 2020, 31, 105902.
[http://dx.doi.org/10.1016/j.dib.2020.105902] [PMID: 32637503]
[8]
Li, D.; Li, Z.; Yang, Y.; Zeng, X.; Li, Y.; Du, X.; Zhu, X. Circular RNAs as biomarkers and therapeutic targets in environmental chemical exposure-related diseases. Environ. Res., 2020, 180, 108825.
[http://dx.doi.org/10.1016/j.envres.2019.108825] [PMID: 31683121]
[9]
Zhi, X.; Jiang, L.; Li, T.; Song, L.; Wu, L.; Cao, H.; Yang, C. Natural product-based semisynthesis and biological evaluation of thiol/amino-Michael adducts of xanthatin derived from Xanthium strumarium as potential pesticidal agents. Bioorg. Chem., 2020, 97, 103696.
[http://dx.doi.org/10.1016/j.bioorg.2020.103696] [PMID: 32135360]
[10]
Lv, M.; Zhang, Y.; Wang, F.; Zhang, S.; Xu, H. Non-food renewable and bioactive forest products for pest management: Valuation of agricultural properties of podophyllotoxin analogs derived from Podophyllum hexandrum as botanical pesticides. Ind. Crops Prod., 2020, 153, 112608.
[http://dx.doi.org/10.1016/j.indcrop.2020.112608]
[11]
Garrido, I.; Flores, P.; Hellín, P.; Vela, N.; Navarro, S.; Fenoll, J. Solar reclamation of agro-wastewater polluted with eight pesticides by heterogeneous photocatalysis using a modular facility. A case study. Chemosphere, 2020, 249, 126156.
[http://dx.doi.org/10.1016/j.chemosphere.2020.126156] [PMID: 32062216]
[12]
Musarurwa, H.; Tavengwa, N.T. Supramolecular solvent-based micro-extraction of pesticides in food and environmental samples. Talanta, 2021, 223(Pt 1), 121515.
[http://dx.doi.org/10.1016/j.talanta.2020.121515] [PMID: 33303131]
[13]
Yao, Y.; Xie, Y.; Zhao, B.; Zhou, L.; Shi, Y.; Wang, Y.; Sheng, Y.; Zhao, H.; Sun, J.; Cao, H. N-dependent ozonation efficiency over nitrogen-containing heterocyclic contaminants: A combined density functional theory study on reaction kinetics and degradation pathways. Chem. Eng. J., 2020, 382, 122708.
[http://dx.doi.org/10.1016/j.cej.2019.122708]
[14]
Mi, Y.; Zhang, J.; Chen, Y.; Sun, X.; Tan, W.; Li, Q.; Guo, Z. New synthetic chitosan derivatives bearing benzenoid/heterocyclic moieties with enhanced antioxidant and antifungal activities. Carbohydr. Polym., 2020, 249, 116847.
[http://dx.doi.org/10.1016/j.carbpol.2020.116847] [PMID: 32933686]
[15]
Havasi, M.H.; Ressler, A.J.; Parks, E.L.; Cocolas, A.H.; Weaver, A.; Seeram, N.P.; Henry, G.E. Antioxidant and tyrosinase docking studies of heterocyclic sulfide derivatives containing a thymol moiety. Inorg. Chim. Acta, 2020, 505, 119495.
[http://dx.doi.org/10.1016/j.ica.2020.119495]
[16]
Wang, S.; Bao, L.; Song, D.; Wang, J.; Cao, X. Heterocyclic lactam derivatives containing piperonyl moiety as potential antifungal agents. Bioorg. Med. Chem. Lett., 2019, 29(20), 126661.
[http://dx.doi.org/10.1016/j.bmcl.2019.126661] [PMID: 31515187]
[17]
Zimmermann, L.A.; de Moraes, M.H.; da Rosa, R.; de Melo, E.B.; Paula, F.R.; Schenkel, E.P.; Steindel, M.; Bernardes, L.S.C. Synthesis and SAR of new isoxazole-triazole bis-heterocyclic compounds as analogues of natural lignans with antiparasitic activity. Bioorg. Med. Chem., 2018, 26(17), 4850-4862.
[http://dx.doi.org/10.1016/j.bmc.2018.08.025] [PMID: 30173929]
[18]
Wang, S.; Bao, L.; Wang, W.; Song, D.; Wang, J.; Cao, X. Heterocyclic pyrrolizinone and indolizinones derived from natural lactam as potential antifungal agents. Fitoterapia, 2018, 129, 257-266.
[http://dx.doi.org/10.1016/j.fitote.2018.07.013] [PMID: 30056185]
[19]
Önal, H.T.; Yuzer, A.; Ince, M.; Ayaz, F. Photo induced anti-inflammatory activities of a Thiophene substituted subphthalocyanine derivative. Photodiagn. Photodyn. Ther., 2020, 30, 101701.
[http://dx.doi.org/10.1016/j.pdpdt.2020.101701] [PMID: 32184175]
[20]
Muğlu, H.; Yakan, H.; Shouaib, H.A. New 1,3,4-thiadiazoles based on thiophene-2-carboxylic acid: Synthesis, characterization, and antimicrobial activities. J. Mol. Struct., 2020, 1203, 127470.
[http://dx.doi.org/10.1016/j.molstruc.2019.127470]
[21]
Opsenica, I.; Filipovic, V.; Nuss, J.E.; Gomba, L.M.; Opsenica, D.; Burnett, J.C.; Gussio, R.; Solaja, B.A.; Bavari, S. The synthesis of 2,5-bis(4-amidinophenyl)thiophene derivatives providing submicromolar-range inhibition of the botulinum neurotoxin serotype A metalloprotease. Eur. J. Med. Chem., 2012, 53, 374-379.
[http://dx.doi.org/10.1016/j.ejmech.2012.03.043] [PMID: 22516424]
[22]
Parai, M.K.; Panda, G.; Chaturvedi, V.; Manju, Y.K.; Sinha, S. Thiophene containing triarylmethanes as antitubercular agents. Bioorg. Med. Chem. Lett., 2008, 18(1), 289-292.
[http://dx.doi.org/10.1016/j.bmcl.2007.10.083] [PMID: 17997304]
[23]
van Kempen, Z.L.E.; Kummer, L.Y.L.; Wieske, L.; Rispens, T.; Eftimov, F.; Killestein, J. Severe breakthrough COVID-19 after SARS-CoV-2 booster vaccination in an MS patient on ocrelizumab. Neuroimmunol. Reports, 2022, 2, 100072.
[http://dx.doi.org/10.1016/j.nerep.2022.100072]
[24]
Bastián, M.R.; Tejedor, M.R.; Angélica, M.; Núñez, R. Detection of SARS-CoV-2 genomic RNA on surgical masks worn by patients: Proof of conceptPrueba de concepto: Detección de material genético de SARS-CoV-2 en mascarillas quirúrgicas de pacientes. Enferm. Infecc. Microbiol. Clin., 2021, 39, 528-530.
[25]
Bardajee, G.R.; Zamani, M.; Mahmoodian, H.; Elmizadeh, H.; Yari, H.; Jouyandeh, L.; Shirkavand, R.; Sharifi, M. Capability of novel fluorescence DNA-conjugated CdTe/ZnS quantum dots nanoprobe for COVID-19 sensing. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2022, 269, 120702.
[http://dx.doi.org/10.1016/j.saa.2021.120702] [PMID: 34922287]
[26]
Wieske, L.; van Dam, K.P.J.; Steenhuis, M.; Stalman, E.W.; Kummer, L.Y.L.; van Kempen, Z.L.E.; Killestein, J.; Volkers, A.G.; Tas, S.W.; Boekel, L.; Wolbink, G.J.; van der Kooi, A.J.; Raaphorst, J.; Löwenberg, M.; Takkenberg, R.B.; D’Haens, G.R.A.M.; Spuls, P.I.; Bekkenk, M.W.; Musters, A.H.; Post, N.F.; Bosma, A.L.; Hilhorst, M.L.; Vegting, Y.; Bemelman, F.J.; Voskuyl, A.E.; Broens, B.; Sanchez, A.P.; van Els, C.A.C.M.; de Wit, J.; Rutgers, A.; de Leeuw, K.; Horváth, B.; Verschuuren, J.J.G.M.; Ruiter, A.M.; van Ouwerkerk, L.; van der Woude, D.; Allaart, R.C.F.; Teng, Y.K.O.; van Paassen, P.; Busch, M.H.; Jallah, P.B.P.; Brusse, E.; van Doorn, P.A.; Baars, A.E.; Hijnen, D.J.; Schreurs, C.R.G.; van der Pol, W.L.; Goedee, H.S.; Keijzer, S.; Keijser, J.B.D.; Boogaard, A.; Cristianawati, O.; ten Brinke, A.; Verstegen, N.J.M.; Zwinderman, K.A.H.; van Ham, S.M.; Kuijpers, T.W.; Rispens, T.; Eftimov, F.; de Jongh, R.; van de Sandt, C.E.; Kuijper, L.; Duurland, M.; Hagen, R.R.; van den Dijssel, J.; Kreher, C.; Bos, A.; Palomares Cabeza, V.; Konijn, V.A.L.; Elias, G.; Vallejo, J.G.; van Gils, M.J.; Ashhurst, T.M.; Nejentsev, S.; Mirfazeli, E.S. Humoral responses after second and third SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders on immunosuppressants: A cohort study. Lancet Rheumatol., 2022, 4(5), e338-e350.
[http://dx.doi.org/10.1016/S2665-9913(22)00034-0] [PMID: 35317410]
[27]
Ramakrishnan, S.G.; Robert, B.; Salim, A.; Ananthan, P.; Sivaramakrishnan, M.; Subramaniam, S.; Natesan, S.; Suresh, R.; Rajeshkumar, G.; Maran, J.P.; Al-Dhabi, N.A.; Karuppiah, P.; Valan Arasu, M. Nanotechnology based solutions to combat zoonotic viruses with special attention to SARS, MERS, and COVID-19: Detection, protection and medication. Microb. Pathog., 2021, 159, 105133.
[http://dx.doi.org/10.1016/j.micpath.2021.105133] [PMID: 34390768]
[28]
Uzunova, K.; Filipova, E.; Pavlova, V.; Vekov, T. Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2. Biomed. Pharmacother., 2020, 131, 110668.
[http://dx.doi.org/10.1016/j.biopha.2020.110668] [PMID: 32861965]
[29]
Didehban, K.; Vessally, E.; Salary, M.; Edjlali, L.; Babazadeh, M. Synthesis of a variety of key medicinal heterocyclic compounds via chemical fixation of CO2 onto o-alkynylaniline derivatives. J. CO2 Utiliz., 2018, 23, 42-50.
[30]
Bolchi, C.; Bavo, F.; Appiani, R.; Roda, G.; Pallavicini, M. 1,4-Benzodioxane, an evergreen, versatile scaffold in medicinal chemistry: A review of its recent applications in drug design. Eur. J. Med. Chem., 2020, 200, 112419.
[http://dx.doi.org/10.1016/j.ejmech.2020.112419] [PMID: 32502862]
[31]
Hanai, Y.; Yoshizawa, S.; Matsuo, K.; Uekusa, S.; Miyazaki, T.; Nishimura, K.; Mabuchi, T.; Ohashi, H.; Ishii, Y.; Tateda, K.; Yoshio, T.; Nishizawa, K. Evaluation of risk factors for uric acid elevation in COVID-19 patients treated with favipiravir. Diagn. Microbiol. Infect. Dis., 2022, 102(4), 115640.
[http://dx.doi.org/10.1016/j.diagmicrobio.2022.115640] [PMID: 35193798]
[32]
Kinoshita, K.; Matsumoto, K.; Kurauchi, Y.; Hisatsune, A.; Seki, T.; Katsuki, H.A. Nurr1 agonist amodiaquine attenuates inflammatory events and neurological deficits in a mouse model of intracerebral hemorrhage. J. Neuroimmunol., 2019, 330, 48-54.
[http://dx.doi.org/10.1016/j.jneuroim.2019.02.010] [PMID: 30825859]
[33]
Yu, H.M.; Chiu, C.H.; Chen, W.T.; Wu, C.H.; Lin, P.Y.; Huang, Y.Y.; Chen, J.H.; Tzen, K.Y.; Shiue, C.Y.; Lin, W.J. Evaluation of 5-[18F]fluoro-2ʹ-deoxycytidine as a tumor imaging agent: A comparison of [18F]FdUrd, [18F]FLT and [18F]FDG. Appl. Radiat. Isot., 2019, 148, 152-159.
[http://dx.doi.org/10.1016/j.apradiso.2019.03.034] [PMID: 30959352]
[34]
Tan, H.; He, L.; Cheng, Z. Inhibition of eIF4E signaling by ribavirin selectively targets lung cancer and angiogenesis. Biochem. Biophys. Res. Commun., 2020, 529(3), 519-525.
[http://dx.doi.org/10.1016/j.bbrc.2020.05.127] [PMID: 32736668]
[35]
Pauwels, R.; Balzarini, J.; Baba, M.; Snoeck, R.; Schols, D.; Herdewijn, P.; Desmyter, J.; De Clercq, E. Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds. J. Virol. Methods, 1988, 20(4), 309-321.
[http://dx.doi.org/10.1016/0166-0934(88)90134-6] [PMID: 2460479]
[36]
Peyrane, F.; Selisko, B.; Decroly, E.; Vasseur, J.J.; Benarroch, D.; Canard, B.; Alvarez, K. High-yield production of short GpppA- and 7MeGpppA-capped RNAs and HPLC-monitoring of methyltransfer reactions at the guanine-N7 and adenosine-2'O positions. Nucleic Acids Res., 2007, 35(4), e26.
[http://dx.doi.org/10.1093/nar/gkl1119] [PMID: 17259217]
[37]
Chen, M.K.; Du, Y.; Sun, L.; Hsu, J.L.; Wang, Y.H.; Gao, Y.; Huang, J.; Hung, M.C. H2O2 induces nuclear transport of the receptor tyrosine kinase c-MET in breast cancer cells via a membrane-bound retrograde trafficking mechanism. J. Biol. Chem., 2019, 294(21), 8516-8528.
[http://dx.doi.org/10.1074/jbc.RA118.005953] [PMID: 30962283]
[38]
Tran, S.; Truong, T.H.; Narendran, A. Evaluation of COVID-19 vaccine response in patients with cancer: An interim analysis. Eur. J. Cancer, 2021, 159, 259-274.
[http://dx.doi.org/10.1016/j.ejca.2021.10.013] [PMID: 34798454]
[39]
Loschwitz, J.; Jäckering, A.; Keutmann, M.; Olagunju, M.; Eberle, R.J.; Coronado, M.A.; Olubiyi, O.O.; Strodel, B. Novel inhibitors of the main protease enzyme of SARS-CoV-2 identified via molecular dynamics simulation-guided in vitro assay. Bioorg. Chem., 2021, 111, 104862.
[http://dx.doi.org/10.1016/j.bioorg.2021.104862] [PMID: 33862474]
[40]
Bikadi, Z.; Hazai, E. Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDock. J. Cheminform., 2009, 1(1), 15.
[http://dx.doi.org/10.1186/1758-2946-1-15] [PMID: 20150996]
[41]
Lii, J.H.; Allinger, N.L. Molecular mechanics. The MM3 force field for hydrocarbons. 3. The van der Waals’ potentials and crystal data for aliphatic and aromatic hydrocarbons. J. Am. Chem. Soc., 1989, 111(23), 8576-8582.
[http://dx.doi.org/10.1021/ja00205a003]
[42]
Summers, K.L.; Mahrok, A.K.; Dryden, M.D.M.; Stillman, M.J. Structural properties of metal-free apometallothioneins. Biochem. Biophys. Res. Commun., 2012, 425(2), 485-492.
[http://dx.doi.org/10.1016/j.bbrc.2012.07.141] [PMID: 22877750]
[43]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[44]
Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[PMID: 19499576]
[45]
Phillips, J.C.; Braun, R.; Wang, W.; Gumbart, J.; Tajkhorshid, E.; Villa, E.; Chipot, C.; Skeel, R.D.; Kalé, L.; Schulten, K. Scalable molecular dynamics with NAMD. J. Comput. Chem., 2005, 26(16), 1781-1802.
[http://dx.doi.org/10.1002/jcc.20289] [PMID: 16222654]
[46]
Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera?A visualization system for exploratory research and analysis. J. Comput. Chem., 2004, 25(13), 1605-1612.
[http://dx.doi.org/10.1002/jcc.20084] [PMID: 15264254]
[47]
Salentin, S.; Schreiber, S.; Haupt, V.J.; Adasme, M.F.; Schroeder, M.; Schroeder, M. PLIP: Fully automated protein-ligand interaction profiler. Nucleic Acids Res., 2015, 43(W1), W443-W447.
[http://dx.doi.org/10.1093/nar/gkv315] [PMID: 25873628]
[48]
The PyMOL Molecular Graphics System. Version 1.7.6; Schrödinger, LLC, 2015.
[49]
Sohrabi, C.; Alsafi, Z.; O’Neill, N.; Khan, M.; Kerwan, A.; Al-Jabir, A.; Iosifidis, C.; Agha, R. World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19). Int. J. Surg., 2020, 76, 71-76.
[http://dx.doi.org/10.1016/j.ijsu.2020.02.034] [PMID: 32112977]
[50]
Chen, Y.; Liu, Q.; Guo, D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J. Med. Virol., 2020, 92(4), 418-423.
[http://dx.doi.org/10.1002/jmv.25681] [PMID: 31967327]
[51]
Zhou, P.; Lv, J.; Zou, J.; Tian, F.; Shang, Z. Halogen-water-hydrogen bridges in biomolecules. J. Struct. Biol., 2010, 169(2), 172-182.
[http://dx.doi.org/10.1016/j.jsb.2009.10.006] [PMID: 19835958]
[52]
Vasylyeva, V.; Nayak, S.K.; Terraneo, G.; Cavallo, G.; Metrangolo, P.; Resnati, G. Orthogonal halogen and hydrogen bonds involving a peptide bond model. CrystEngComm, 2014, 16(35), 8102-8105.
[http://dx.doi.org/10.1039/C4CE01514B] [PMID: 25663816]
[53]
Hardegger, L.A.; Kuhn, B.; Spinnler, B.; Anselm, L.; Ecabert, R.; Stihle, M.; Gsell, B.; Thoma, R.; Diez, J.; Benz, J.; Plancher, J.M.; Hartmann, G.; Banner, D.W.; Haap, W.; Diederich, F. Systematic investigation of halogen bonding in protein-ligand interactions. Angew. Chem. Int. Ed., 2011, 50(1), 314-318.
[http://dx.doi.org/10.1002/anie.201006781] [PMID: 21184410]
[54]
Vallejos, M.; Auffinger, P.; Ho, P.S. Halogen interactions in biomolecular crystal structures. Int. Tables Crystallogr., 2012, F, 821-826.
[55]
Maillard, M.C.; Hom, R.K.; Benson, T.E.; Moon, J.B.; Mamo, S.; Bienkowski, M.; Tomasselli, A.G.; Woods, D.D.; Prince, D.B.; Paddock, D.J.; Emmons, T.L.; Tucker, J.A.; Dappen, M.S.; Brogley, L.; Thorsett, E.D.; Jewett, N.; Sinha, S.; John, V. Design, synthesis, and crystal structure of hydroxyethyl secondary amine-based peptidomimetic inhibitors of human beta-secretase. J. Med. Chem., 2007, 50(4), 776-781.
[http://dx.doi.org/10.1021/jm061242y] [PMID: 17300163]
[56]
Iltzsch, M.H.; Uber, S.S.; Tankersley, K.O.; el Kouni, M.H. Structure-activity relationship for the binding of nucleoside ligands to adenosine kinase from Toxoplasma gondii. Biochem. Pharmacol., 1995, 49(10), 1501-1512.
[http://dx.doi.org/10.1016/0006-2952(95)00029-Y] [PMID: 7763293]
[57]
Parks, D.J.; Lafrance, L.V.; Calvo, R.R.; Milkiewicz, K.L.; Gupta, V.; Lattanze, J.; Ramachandren, K.; Carver, T.E.; Petrella, E.C.; Cummings, M.D.; Maguire, D.; Grasberger, B.L.; Lu, T. 1,4-Benzodiazepine-2,5-diones as small molecule antagonists of the HDM2-p53 interaction: Discovery and SAR. Bioorg. Med. Chem. Lett., 2005, 15, 765-770.
[58]
Benjahad, A.; Guillemont, J.; Andries, K.; Nguyen, C.H.; Grierson, D.S. 3-Iodo-4-phenoxypyridinones (IOPY’s), a new family of highly potent non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg. Med. Chem. Lett., 2003, 13(24), 4309-4312.
[http://dx.doi.org/10.1016/j.bmcl.2003.09.045] [PMID: 14643315]
[59]
Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The protein data bank. Nucleic Acids Res., 2000, 28(1), 235-242.
[http://dx.doi.org/10.1093/nar/28.1.235] [PMID: 10592235]
[60]
Howard, E.I.; Sanishvili, R.; Cachau, R.E.; Mitschler, A.; Chevrier, B.; Barth, P.; Lamour, V.; Van Zandt, M.; Sibley, E.; Bon, C.; Moras, D.; Schneider, T.R.; Joachimiak, A.; Podjarny, A. Ultrahigh resolution drug design I: Details of interactions in human aldose reductase-inhibitor complex at 0.66 Å. Proteins, 2004, 55(4), 792-804.
[http://dx.doi.org/10.1002/prot.20015] [PMID: 15146478]
[61]
Hardegger, L.A.; Kuhn, B.; Spinnler, B.; Anselm, L.; Ecabert, R.; Stihle, M.; Gsell, B.; Thoma, R.; Diez, J.; Benz, J.; Plancher, J.M.; Hartmann, G.; Isshiki, Y.; Morikami, K.; Shimma, N.; Haap, W.; Banner, D.W.; Diederich, F. Halogen bonding at the active sites of human cathepsin L and MEK1 kinase: Efficient interactions in different environments. ChemMedChem, 2011, 6(11), 2048-2054.
[http://dx.doi.org/10.1002/cmdc.201100353] [PMID: 21898833]
[62]
Chockalingam, A.; Gnanavelu, G.; Venkatesan, S.; Elangovan, S.; Jagannathan, V.; Subramaniam, T.; Alagesan, R.; Dorairajan, S. Efficacy and optimal dose of sildenafil in primary pulmonary hypertension. Int. J. Cardiol., 2005, 99(1), 91-95.
[http://dx.doi.org/10.1016/j.ijcard.2003.12.023] [PMID: 15721505]
[63]
Xu, Z.; Liu, Z.; Chen, T.; Chen, T.; Wang, Z.; Tian, G.; Shi, J.; Wang, X.; Lu, Y.; Yan, X.; Wang, G.; Jiang, H.; Chen, K.; Wang, S.; Xu, Y.; Shen, J.; Zhu, W. Utilization of halogen bond in lead optimization: A case study of rational design of potent phosphodiesterase type 5 (PDE5) inhibitors. J. Med. Chem., 2011, 54(15), 5607-5611.
[http://dx.doi.org/10.1021/jm200644r] [PMID: 21714539]
[64]
Sung, B.J.; Yeon Hwang, K.; Ho Jeon, Y.; Lee, J.I.; Heo, Y.S.; Hwan Kim, J.; Moon, J.; Min Yoon, J.; Hyun, Y.L.; Kim, E.; Jin Eum, S.; Park, S.Y.; Lee, J.O.; Gyu Lee, T.; Ro, S.; Myung Cho, J.; Lee, J.O.; Lee, T.G.; Ro, S.; Cho, J.M. Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. Nature, 2003, 425(6953), 98-102.
[http://dx.doi.org/10.1038/nature01914] [PMID: 12955149]
[65]
Raha, K.; Peters, M.B.; Wang, B.; Yu, N.; Wollacott, A.M.; Westerhoff, L.M.; Merz, K.M., Jr The role of quantum mechanics in structure-based drug design. Drug Discov. Today, 2007, 12(17-18), 725-731.
[http://dx.doi.org/10.1016/j.drudis.2007.07.006] [PMID: 17826685]
[66]
Mendez, L.; Henriquez, G.; Sirimulla, S.; Narayan, M. Looking back, looking forward at halogen bonding in drug discovery. Molecules, 2017, 22(9), 1397-1412.
[http://dx.doi.org/10.3390/molecules22091397] [PMID: 28837116]
[67]
Halvorson, H.O.; Quezada, F. Marine biotechnology. In: Encyclopedia of Ocean Sciences, 2nd ed; Steele, J.H., Ed.; Academic Press: Oxford, 2009; pp. 560-566.
[http://dx.doi.org/10.1016/B978-012374473-9.00772-4]
[68]
Puranik, N.V.; Rani, R.; Singh, V.A.; Tomar, S.; Puntambekar, H.M.; Srivastava, P. Evaluation of the antiviral potential of halogenated dihydrorugosaflavonoids and molecular modeling with nsP3 protein of chikungunya virus (CHIKV). ACS Omega, 2019, 4(23), 20335-20345.
[http://dx.doi.org/10.1021/acsomega.9b02900] [PMID: 31815237]
[69]
Mohareb, R.M.; Abdallah, A.E.M.; Abdelaziz, M.A. New approaches for the synthesis of pyrazole, thiophene, thieno[2,3-b]pyridine, and thiazole derivatives together with their anti-tumor evaluations. Med. Chem. Res., 2014, 23(2), 564-579.
[http://dx.doi.org/10.1007/s00044-013-0664-7]
[70]
Mohareb, R.M.; Wardakhan, W.W.; Hamed, F.I. Synthesis and cytotoxicity of fused thiophene and pyrazole derivatives derived from 2-N-acetyl-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene. Med. Chem. Res., 2015, 24(5), 2043-2054.
[http://dx.doi.org/10.1007/s00044-014-1273-9]
[71]
Mohareb, R.M.; Zaki, M.Y.; Abbas, N.S. Synthesis, anti-inflammatory and anti-ulcer evaluations of thiazole, thiophene, pyridine and pyran derivatives derived from androstenedione. Steroids, 2015, 98, 80-91.
[http://dx.doi.org/10.1016/j.steroids.2015.03.001] [PMID: 25759119]
[72]
Dömling, A. Recent developments in isocyanide based multicomponent reactions in applied chemistry. Chem. Rev., 2006, 106(1), 17-89.
[http://dx.doi.org/10.1021/cr0505728] [PMID: 16402771]
[73]
Rivera, D.G.; León, F.; Concepción, O.; Morales, F.E.; Wessjohann, L.A. A multiple multicomponent approach to chimeric peptide-peptoid podands. Chemistry, 2013, 19(20), 6417-6428.
[http://dx.doi.org/10.1002/chem.201201591] [PMID: 23512744]
[74]
Ugi, I.; Werner, B.; Dömling, A. The chemistry of isocyanides, their multi-component reactions and their libraries. Molecules, 2003, 8(1), 53-66.
[http://dx.doi.org/10.3390/80100053]
[75]
van Berkel, S.S.; Bögels, B.G.M.; Wijdeven, M.A.; Westermann, B.; Rutjes, F.P.J.T. Recent advances in asymmetric isocyanide-based multi-component reactions. Eur. J. Org. Chem., 2012, 2012(19), 3543-3559.
[http://dx.doi.org/10.1002/ejoc.201200030]
[76]
Darbarwar, M.; Sundaramurthy, V. Synthesis of coumarins with 3:4-fused ringsystems and their physiological activity. Synthesis, 1982, 1982(5), 337-388.
[http://dx.doi.org/10.1055/s-1982-29806]
[77]
Kemnitzer, W.; Drewe, J.; Jiang, S.; Zhang, H.; Wang, Y.; Zhao, J.; Jia, S.; Herich, J.; Labreque, D.; Storer, R.; Meerovitch, K.; Bouffard, D.; Rej, R.; Denis, R.; Blais, C.; Lamothe, S.; Attardo, G.; Gourdeau, H.; Tseng, B.; Kasibhatla, S.; Cai, S.X. Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 1. Structure-activity relationships of the 4-aryl group. J. Med. Chem., 2004, 47(25), 6299-6310.
[http://dx.doi.org/10.1021/jm049640t] [PMID: 15566300]