Copyright (c) 2024 Ashish Mullani, Manoj Charde
This work is licensed under a Creative Commons Attribution 4.0 International License.
Design, Synthesis and Biological Evaluation of Pyridyltriazole Derivatives as Potent Antitubercular Agents
Corresponding Author(s) : Ashish K. Mullani
Asian Journal of Chemistry,
Vol. 36 No. 11 (2024): Vol 36 Issue 11, 2024
Abstract
In current investigation, a new series of pyridyltriazole derivatives were synthesized by conventional methods and characterized through spectroscopic techniques such as IR, NMR (1H) and mass spectroscopy. Based on colour observation and percentage of inhibition, all 24 pyridyltriazole derivatives were subjected to in vitro anti-mycobacterial testing using MABA techniques against the Mycobacterium tuberculosis (H37Rv) strain. It was found that all of the synthesized compounds were efficient in suppressing the M. tuberculosis H37Rv strain at concentrations of 1, 5 and 10 µg/mL. Among all the synthesized compounds, only 2, 3, 6, 7, 8, 11, 14, 15, 18, 20, 21, 22, 23, 24 has good anti-TB efficacy in contrast to the standard medication. According to the in silico ADME prediction, every synthesized molecule has drug-like qualities and is appropriate for oral bioavailability. Furthermore, research utilizing molecular docking have been conducted to get mechanistic understanding and molecular interactions in opposition to the mycobacterial InhA enzyme. Utilizing a molecular docking analysis, hits against specific molecular targets were found. This in silico study delved into the molecular interactions between potential compounds and the Mtbenoyl-reductaseInhA (PDB 5JFO).
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A. Koul, E. Arnoult, N. Lounis, J. Guillemont and K. Andries, Nature, 469, 483 (2011); https://doi.org/10.1038/nature09657
J.R. Glynn, P. Khan, T. Mzembe, L. Sichali, P.E.M. Fine, A.C. Crampin and R.M.G.J. Houben, PLoS One, 18, e0278136 (2023); https://doi.org/10.1371/journal.pone.0278136
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T. Masini, J. Furin, Z. Udwadia and L. Guglielmetti, Indian J. Med. Res., 157, 220 (2023); https://doi.org/10.4103/ijmr.ijmr_300_23
M. Singh, M. Jeyaraman, N. Jeyaraman, T. Jayakumar, K.P. Iyengar and V.K. Jain, J. Clin. Orthop. Trauma, 44, 102257 (2023); https://doi.org/10.1016/j.jcot.2023.102257
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T.R. Walsh, A.C. Gales, R. Laxminarayan and P.C. Dodd, PLoS Med., 20, e1004264 (2023); https://doi.org/10.1371/journal.pmed.1004264
M. Pattnaik, S. Pattnaik, J. Pradhan and D. Bhattacharya, Int. J. Community Med. Public Health, 10, 4485 (2023); https://doi.org/10.18203/2394-6040.ijcmph20233499
M. Alcaraz, T.E. Edwards and L. Kremer, Expert Rev. Anti Infect. Ther., 21, 813 (2023); https://doi.org/10.1080/14787210.2023.2224563
C. Bussi and M.G. Gutierrez, FEMS Microbiol. Rev., 43, 341 (2019); https://doi.org/10.1093/femsre/fuz006
H. Marrakchi, M.A. Lanéelle and M. Daffé, Chem. Biol., 21, 67 (2014); https://doi.org/10.1016/j.chembiol.2013.11.011
K. Takayama, C. Wang and G.S. Besra, Clin. Microbiol. Rev., 18, 81 (2005); https://doi.org/10.1128/cmr.18.1.81-101.2005
G. Kumar and S. Kapoor, Bioorg. Med. Chem., 81, 117212 (2023); https://doi.org/10.1016/j.bmc.2023.117212
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M. Zala, J.J. Vora and V.M. Khedkar, ACS Omega, 8, 20262 (2023); https://doi.org/10.1021/acsomega.2c07267
M.M. Ghorab, M.S.A. El-Gaby, A.M. Soliman, M.S. Alsaid, M.M. Abdel-Aziz and M.M. Elaasser, Chem. Cent. J., 11, 42 (2017); https://doi.org/10.1186/s13065-017-0271-7
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C. Prabhu, Int. J. Curr. Pharm. Res., 10, 29 (2018); https://doi.org/10.22159/ijcpr.2018v10i4.28455
R. Singh, S.K. Kashaw, V.K. Mishra, M. Mishra, V. Rajoriya and V. Kashaw, Indian J. Pharm. Sci., 80, 36 (2018); https://doi.org/10.4172/pharmaceutical-sciences.1000328
J. Ahirwar, D. Ahirwar, S. Lanjhiyana and A.K. Jha, Int. J. Pharm. Clin. Res., 9, 702 (2017).
K.P. Barot, K.S. Manna and M.D. Ghate, J. Saudi Chem. Soc., 21, S35 (2017); https://doi.org/10.1016/j.jscs.2013.09.010
Y. Sajja, H.R. Vulupala, L. Nagarapu, S.B. Vasamsetti, S. Kotamraju, R. Bantu and J.B. Nanubolu, Bioorg. Med. Chem. Lett., 26, 858 (2016); https://doi.org/10.1016/j.bmcl.2015.12.078
F. Afreen, Int. J. Pharm. Chem., 5, 352 (2015).
S. Rathod, K. Shinde, J. Porlekar, P. Choudhari, R. Dhavale, D. Mahuli, Y. Tamboli, M. Bhatia, K.P. Haval, A.G. Al-Sehemi and M. Pannipara, ACS Omega, 8, 391 (2022); https://doi.org/10.1021/acsomega.2c04837
A.D. Hunter, J. Chem. Educ., 74, 905 (1997); https://doi.org/10.1021/ed074p905
I.A. Guedes, C.S. de Magalhães and L.E. Dardenne, Biophys. Rev., 6, 75 (2013); https://doi.org/10.1007/s12551-013-0130-2
M.A. Alamri, J. Mol. Liq., 330, 115699 (2021); https://doi.org/10.1016/j.molliq.2021.115699
N.K. Taneja and J.S. Tyagi, J. Antimicrob. Chemother., 60, 288 (2007); https://doi.org/10.1093/jac/dkm207