Synthesis and Molecular Docking Studies of N’-benzoylsalicylhydrazide derivatives as antituberculosis through InHA enzym inhibition
The specific aims of this study is to synthesize and to study the possible mechanism of N’-benzoylsalicylhydrazide derivatives as an antituberculosis agent through InhA (Enoyl acyl carrier protein reductase) inhibition using in silico method. Five analogues of N’-benzoylsalicylhydrazide were synthesized using microwave irradiation from methyl salicylate as starting material, which yielded 80-90% product on average. This indicates a considerable improvement in terms of effectivity and efficiency, compared to the more conventional method using reflux condition. Character-ization of the compounds were subsequently carried out by UV, FTIR, 1H-NMR, 13C-NMR spectroscopy, which confirmed that the compounds had been successfully synthesized. Ultimately, molecular docking was performed using Molegro Virtual Docker (MVD) on the active site of InhA enzyme to predict the activity of the compounds. The results showed that all compounds performed comparatively well against N-(4-Methylbenzoyl)-4-benzylpiperidine as the native ligand and also yielded lower docking score than isoniazide (INH). From this study it can be concluded that N’-benzoylsalicylhydrazide derivatives could be synthesized using microwave irradiation with good product yield and all of the synthesized analogues are suggested to possess antituberculosis activity via InhA enzyme inhibition. In vitro activity will have to be determined in the future to validate whether N’-benzoylsalicylhydrazide derivatives perform well as a potential antituberculosis agent.
Dipiro, Joseph., Robert L., Gary C., Gary R.,Barbara G., L. Michael P. 2008. Pharmacotherapy: apathophysiologic approach 7th. New York,McGraw-Hill Medical. pp 1839-2096.
Halgren, Thomas A. 1996. Merck Molecular Force Field. I Basis, form, scope, parametrization, and performance of MMFF94. J. Com. Chem. 17(5-6): 490-519.
He, Xin., Alian, A., Montellano, P. R. O. 2007. Inhibition of the Mycobacterium tuberculosis enoyl acyl carrier protein reductase InhA by arylamides. Bioorg Med Chem. 15(21): 6649–6658
Indonesian Ministry of Health. 2013. Riset Kesehatan Dasar.
Katzung, B.G., Masters, S.B., Trevor, A.J. 2009. Basic & Clinical Pharmacology Edition 11th. New York: McGraw-Hill Companies. pp 1089-1093
Kumar, Pradeep., Narasimhan, B., Ramasamy, K., Mani, V., Mishra, R.K., Majeed, A.B.A. 2014. Synthesis, antimicrobial, anticancer evaluation and QSAR studies of 2/3-bromo-N0-(substituted benzylidene/3-phenylallylidene)-benzohydrazides. Arabian Journal of Chemistry. XXX.
Lourenço, Maria C. S., Souza, M.V.N., Pinheiro, A, C., Ferreira, M. L., Gonçalves, R. S. B., Nogueira, T. C., Peralta, M. A. 2007. Evaluation of anti-tubercular activity of nicotinic and isoniazid analogues. ARKIVOC (xv) 181-191
Maheswari, R., Manjula, J. 2015. Synthesis, Characterization and Biological Applications of Benzohydrazide derivatives. International Journal of Applied Research. 1(10): 587-592
Pietrangelo, Ann., Holland, K. The Top 10 Deadliest Diseases. 2017. Retrieved: September 5th, 2018, from https://www.healthline.com/health/top-10-deadliest-diseases#cad
Thomas, Asha B., Nanda, R. K., Kothapalli, L.P., Deshpande, A. V. 2011. Synthesis and Antimicrobial Activity of N-[2-(aryl/substituted aryl)-4-oxo-1,3-thiazolidin-3-yl]pyridine-4-carboxamide. Journal of the Korean Chemical Society. 55, 6, 960-968
Thomsen, René., Christensen, M. H. 2006. MolDock: A New Technique for High-Accuracy Molecular Docking. J. Med. Chem. 49: 3315-3321.
Widiyana, Anita Puspa., Putra, G.S., Sulistyowaty, M. I., Hardjono, S., Budiati, T. 2017. Method Optimization of 2,3-Disubtitutedquinazolin-4(3H)-One Derivatives. Journal of Chemical and Pharmaceutical Research. 9(8):24-28
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