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Synthesis, docking and ADMET prediction of novel 5-((5-substituted-1-H-1,2,4-triazol-3-yl) methyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine as antifungal agents

Jaiprakash N. Sangshetti ,  Firoz A. Kalam Khan ,  Rashmi S. Chouthe ,  Manoj G. Damale ,  Devanand B. Shinde

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Citation:  Jaiprakash N. Sangshetti, Firoz A. Kalam Khan, Rashmi S. Chouthe, Manoj G. Damale, Devanand B. Shinde. Synthesis, docking and ADMET prediction of novel 5-((5-substituted-1-H-1,2,4-triazol-3-yl) methyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine as antifungal agents[J]. Chinese Chemical Letters, 2014, 25(7): 1033-1038. doi: 10.1016/j.cclet.2014.04.003 shu

Synthesis, docking and ADMET prediction of novel 5-((5-substituted-1-H-1,2,4-triazol-3-yl) methyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine as antifungal agents

    • 通讯作者: Jaiprakash N. Sangshetti,
  • 基金项目:

    Dr. Zahid Zaheer, Incharge Principal, Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431 001 (M.S.) (M.S.)

摘要: A novel series of 5-((5-substituted-1H-1,2,4-triazol-3-yl)methyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridines 5(a-i) has been synthesized from thienopyridine hydrazide, substituted aromatic nitriles using 4-dimethylaminopyridine (DMAP) as a catalyst under microwave irradiation and evaluated for their in vitro antifungal activity. Compound 5g is found to be more potent against Candida albicans when compared with miconazole. Docking study of the newly synthesized compounds was performed, and results showed good binding mode in the active site of fungal enzyme P450 cytochrome lanosterol 14ademethylase. ADMET properties of synthesized compounds were also analyzed and showed good drug like properties. The results of in vitro antifungal activity, docking study and ADMET prediction revealed that the synthesized compounds have potential antifungal activity and can be further optimized and developed as a lead compound.

English

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    1. [1] D.J. Sheehan, C.A. Hitchcock, C.M. Sibley, Current and emerging azole antifungal agents, Clin. Microbiol. Rev. 12 (1999) 40-79.[1] D.J. Sheehan, C.A. Hitchcock, C.M. Sibley, Current and emerging azole antifungal agents, Clin. Microbiol. Rev. 12 (1999) 40-79.

    2. [2] R. Cha, J.D. Sobel, Fluconazole for the treatment of candidiasis: 15 years experience, Expert Rev. Anti. Infect. Ther. 2 (2004) 357-366.[2] R. Cha, J.D. Sobel, Fluconazole for the treatment of candidiasis: 15 years experience, Expert Rev. Anti. Infect. Ther. 2 (2004) 357-366.

    3. [3] N.H. Georgopapadakou, T.J. Walsh, Antifungal agents: chemotherapeutic targets and immunologic strategies, Antimicrob. Agents Chemother. 40 (1996) 279-291.[3] N.H. Georgopapadakou, T.J. Walsh, Antifungal agents: chemotherapeutic targets and immunologic strategies, Antimicrob. Agents Chemother. 40 (1996) 279-291.

    4. [4] M.A. Pfaller, S.A. Messer, R.J. Hollis, et al., In vitro activities of posaconazole (Sch 56592) compared with those of itraconazole and fluconazole against 3685 clinical isolates of Candida spp. and Cryptococcus neoformans, Antimicrob. Agents Chemother. 45 (2001) 2862-2864.[4] M.A. Pfaller, S.A. Messer, R.J. Hollis, et al., In vitro activities of posaconazole (Sch 56592) compared with those of itraconazole and fluconazole against 3685 clinical isolates of Candida spp. and Cryptococcus neoformans, Antimicrob. Agents Chemother. 45 (2001) 2862-2864.

    5. [5] L. Jeu, F.J. Piacenti, A.G. Lyakhovetskiy, H.B. Fung, Voriconazole, Clin. Ther. 25 (2003) 1321-1381.[5] L. Jeu, F.J. Piacenti, A.G. Lyakhovetskiy, H.B. Fung, Voriconazole, Clin. Ther. 25 (2003) 1321-1381.

    6. [6] G.I. Lepesheva, N.G. Zaitseva, W.D. Nes, et al., CYP51 from Trypanosoma cruzi: a phyla-specific residue in the B0 helix defines substrate preferences of sterol 14ademethylase, J. Biol. Chem. 281 (2006) 3577-3585.[6] G.I. Lepesheva, N.G. Zaitseva, W.D. Nes, et al., CYP51 from Trypanosoma cruzi: a phyla-specific residue in the B0 helix defines substrate preferences of sterol 14ademethylase, J. Biol. Chem. 281 (2006) 3577-3585.

    7. [7] K. Liaras, J. Geronikaki, J. Glamočlija, A.Ćirić,M. Soković, Thiazole-based chalcones as potent antimicrobial agents: synthesis and biological evaluation, Bioorg. Med. Chem. 19 (2011) 3135-3140.[7] K. Liaras, J. Geronikaki, J. Glamočlija, A.Ćirić,M. Soković, Thiazole-based chalcones as potent antimicrobial agents: synthesis and biological evaluation, Bioorg. Med. Chem. 19 (2011) 3135-3140.

    8. [8] R.G. Kalkhambkar, G.M. Kulkarni, H. Shivkumar, R.R. Nagendra, Synthesis of novel triheterocyclic thiazoles as anti-inflammatory and analgesic agents, Eur. J. Med. Chem. 42 (2007) 1272-1276.[8] R.G. Kalkhambkar, G.M. Kulkarni, H. Shivkumar, R.R. Nagendra, Synthesis of novel triheterocyclic thiazoles as anti-inflammatory and analgesic agents, Eur. J. Med. Chem. 42 (2007) 1272-1276.

    9. [9] A.B. Scheiff, S.G. Yerande, A. El-Tayeb, et al., 2-Amino-5-benzoyl-4-phenylthiazoles: development of potent and selective adenosine A1 receptor antagonists, Bioorg. Med. Chem. 18 (2010) 2195-2203.[9] A.B. Scheiff, S.G. Yerande, A. El-Tayeb, et al., 2-Amino-5-benzoyl-4-phenylthiazoles: development of potent and selective adenosine A1 receptor antagonists, Bioorg. Med. Chem. 18 (2010) 2195-2203.

    10. [10] Y. Jiang, J. Zhang, Y. Cao, et al., Synthesis, in vitro evaluation and molecular docking studies of new triazole derivatives as antifungal agents, Bioorg. Med. Chem. Lett. 21 (2011) 4471-4475.[10] Y. Jiang, J. Zhang, Y. Cao, et al., Synthesis, in vitro evaluation and molecular docking studies of new triazole derivatives as antifungal agents, Bioorg. Med. Chem. Lett. 21 (2011) 4471-4475.

    11. [11] X. Chai, J. Zhang, Y. Cao, et al., Design, synthesis and molecular docking studies of novel triazole as antifungal agent, Eur. J. Med. Chem. 46 (2011) 3167-3176.[11] X. Chai, J. Zhang, Y. Cao, et al., Design, synthesis and molecular docking studies of novel triazole as antifungal agent, Eur. J. Med. Chem. 46 (2011) 3167-3176.

    12. [12] P.H. Olesen, A.R. Sorensen, B. Urso, et al., Synthesis and in vitro characterization of 1-(4-aminofurazan-3-yl)-5-dialkylaminomethyl-1H-[1,2,3]triazole-4-carboxylic acid derivatives: a new class of selective GSK-3 inhibitors, J. Med. Chem. 46 (2003) 3333-3341.[12] P.H. Olesen, A.R. Sorensen, B. Urso, et al., Synthesis and in vitro characterization of 1-(4-aminofurazan-3-yl)-5-dialkylaminomethyl-1H-[1,2,3]triazole-4-carboxylic acid derivatives: a new class of selective GSK-3 inhibitors, J. Med. Chem. 46 (2003) 3333-3341.

    13. [13] H.J. Breslin, T.A. Miskowski, M.J. Kukla, et al., Tripeptidyl-peptidase II (TPP II) inhibitory activity of (S)-2,3-dihydro-2-(1H-imidazol-2-yl)-1H-indoles, a systematic SAR evaluation. Part 2, Bioorg. Med. Chem. Lett. 13 (2003) 4467-4471.[13] H.J. Breslin, T.A. Miskowski, M.J. Kukla, et al., Tripeptidyl-peptidase II (TPP II) inhibitory activity of (S)-2,3-dihydro-2-(1H-imidazol-2-yl)-1H-indoles, a systematic SAR evaluation. Part 2, Bioorg. Med. Chem. Lett. 13 (2003) 4467-4471.

    14. [14] J.J. Baldwin, P.A. Kasinger, F.C. Novello, et al., 4-Trifluoromethylimidazoles and 5-(4-pyridyl)-1,2,4-triazoles, new classes of xanthine oxidase inhibitors, J. Med. Chem. 18 (1975) 895-900.[14] J.J. Baldwin, P.A. Kasinger, F.C. Novello, et al., 4-Trifluoromethylimidazoles and 5-(4-pyridyl)-1,2,4-triazoles, new classes of xanthine oxidase inhibitors, J. Med. Chem. 18 (1975) 895-900.

    15. [15] Y. Kap-Sun, E. Michelle, J.F. Farkas, N.A. Meanwell, A base-catalyzed, direct synthesis of 3,5-disubstituted 1,2,4-triazoles from nitriles and hydrazides, Tetrahedron Lett. 46 (2005) 3429-3432.[15] Y. Kap-Sun, E. Michelle, J.F. Farkas, N.A. Meanwell, A base-catalyzed, direct synthesis of 3,5-disubstituted 1,2,4-triazoles from nitriles and hydrazides, Tetrahedron Lett. 46 (2005) 3429-3432.

    16. [16] J.N. Sangshetti, A.R. Chabukswar, D.B. Shinde, et al., Microwave assisted one pot synthesis of some novel 2,5-disubstituted 1,3,4-oxadiazoles as antifungal agents, Bioorg. Med. Chem. Lett. 21 (2011) 444-448.[16] J.N. Sangshetti, A.R. Chabukswar, D.B. Shinde, et al., Microwave assisted one pot synthesis of some novel 2,5-disubstituted 1,3,4-oxadiazoles as antifungal agents, Bioorg. Med. Chem. Lett. 21 (2011) 444-448.

    17. [17] J.N. Sangshetti, D.B. Shinde, One pot synthesis and SAR of some novel 3-substituted 5,6-diphenyl-1,2,4-triazines as antifungal agents, Bioorg. Med. Chem. Lett. 20 (2010) 742-745.[17] J.N. Sangshetti, D.B. Shinde, One pot synthesis and SAR of some novel 3-substituted 5,6-diphenyl-1,2,4-triazines as antifungal agents, Bioorg. Med. Chem. Lett. 20 (2010) 742-745.

    18. [18] J.N. Sangshetti, R.R. Nagawade, D.B. Shinde, Synthesis of novel 3-(1-(1-substituted piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-1,2,4-oxadiazol-5(4H)-one as antifungal agents, Bioorg. Med. Chem. Lett. 19 (2009) 3564-3567.[18] J.N. Sangshetti, R.R. Nagawade, D.B. Shinde, Synthesis of novel 3-(1-(1-substituted piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-1,2,4-oxadiazol-5(4H)-one as antifungal agents, Bioorg. Med. Chem. Lett. 19 (2009) 3564-3567.

    19. [19] J.N. Sangshetti, D.B. Shinde, Synthesis and SAR of some new 4-substituted 3H-1,2,3,5-oxathiadiazole 2-oxides as antifungal agents, Lett. Drug Des. Discov. 7 (2010) 171-175.[19] J.N. Sangshetti, D.B. Shinde, Synthesis and SAR of some new 4-substituted 3H-1,2,3,5-oxathiadiazole 2-oxides as antifungal agents, Lett. Drug Des. Discov. 7 (2010) 171-175.

    20. [20] J.N. Sangshetti, D.B. Shinde, Synthesis of some novel 3-(1-(1-substitutedpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-5-substituted phenyl-1,2,4-oxadiazoles as antifungal agents, Eur. J. Med. Chem. 46 (2011) 1040-1044.[20] J.N. Sangshetti, D.B. Shinde, Synthesis of some novel 3-(1-(1-substitutedpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-5-substituted phenyl-1,2,4-oxadiazoles as antifungal agents, Eur. J. Med. Chem. 46 (2011) 1040-1044.

    21. [21] J.N. Sangshetti, D.B. Shinde, A.P. Sarkate, Synthesis, antifungal activity and docking study of some new 1,2,4-triazole analogs, Chem. Biol. Drug Des. 78 (2011) 800-809.[21] J.N. Sangshetti, D.B. Shinde, A.P. Sarkate, Synthesis, antifungal activity and docking study of some new 1,2,4-triazole analogs, Chem. Biol. Drug Des. 78 (2011) 800-809.

    22. [22] V.P. Modi, P.N. Patel, H.S. Patel, Synthesis, spectral investigation and biological evaluation of novel noncytotoxic tetrahydrothieno [3,2-c]pyridine hydrazide derivatives, Der Pharmacia Lett. 3 (2011) 120-133.[22] V.P. Modi, P.N. Patel, H.S. Patel, Synthesis, spectral investigation and biological evaluation of novel noncytotoxic tetrahydrothieno [3,2-c]pyridine hydrazide derivatives, Der Pharmacia Lett. 3 (2011) 120-133.

    23. [23] J.N. Sangshetti, P.D. Priyanka, S.C. Rashmi, et al., Microwave assisted nano (ZnO-TiO2) catalyzed synthesis of some new 4,5,6,7-tetrahydro-6-((5-substituted-1,3,4-oxadiazol-2-yl) methyl) thieno[2,3-c] pyridine as antimicrobial agents, Bioorg. Med. Chem. Lett. 23 (2013) 2250-2253.[23] J.N. Sangshetti, P.D. Priyanka, S.C. Rashmi, et al., Microwave assisted nano (ZnO-TiO2) catalyzed synthesis of some new 4,5,6,7-tetrahydro-6-((5-substituted-1,3,4-oxadiazol-2-yl) methyl) thieno[2,3-c] pyridine as antimicrobial agents, Bioorg. Med. Chem. Lett. 23 (2013) 2250-2253.

    24. [24] D. Greenwood, R.C.B. Slack, J.F. Peutherer, Medical Microbiology, 4th ed., ELBS, London, 1992.[24] D. Greenwood, R.C.B. Slack, J.F. Peutherer, Medical Microbiology, 4th ed., ELBS, London, 1992.

    25. [25] R.W. Hooft, G. Vriend, C. Sander, E.E. Abola, Errors in protein structures, Nature 381 (1996) 272.[25] R.W. Hooft, G. Vriend, C. Sander, E.E. Abola, Errors in protein structures, Nature 381 (1996) 272.

    26. [26] VLife Molecular Design Suite 4.3, VLife Sciences Technologies Pvt. Ltd., www.Vlifesciences. com.[26] VLife Molecular Design Suite 4.3, VLife Sciences Technologies Pvt. Ltd., www.Vlifesciences. com.

    27. [27] D. Lagorce, H. Sperandio, M.A. Miteva, et al., FAF-Drugs2: free ADME/tox filtering tool to assist drug discovery and chemical biology projects, BMC Bioinformatics 9 (2008) 396.[27] D. Lagorce, H. Sperandio, M.A. Miteva, et al., FAF-Drugs2: free ADME/tox filtering tool to assist drug discovery and chemical biology projects, BMC Bioinformatics 9 (2008) 396.

    28. [28] C.A. Lipinski, F. Lombardo, B.W. Dominy, et al., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Adv. Drug Deliv. Rev. 46 (2001) 3-26.[28] C.A. Lipinski, F. Lombardo, B.W. Dominy, et al., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Adv. Drug Deliv. Rev. 46 (2001) 3-26.

    29. [29] P. Ertl, B. Rohde, P. Selzer, Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties, J. Med. Chem. 43 (2000) 3714-3717.[29] P. Ertl, B. Rohde, P. Selzer, Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties, J. Med. Chem. 43 (2000) 3714-3717.

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  • 收稿日期:  2014-01-20
  • 网络出版日期:  2014-03-28
通讯作者: 陈斌, bchen63@163.com
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