IN SILICO STUDY FOR IDENTIFICATION OF DRUG LIKE INHIBITOR FROM NATURAL COMPOUNDS AGAINST INHA REDUCTASE OF MYCOBACTERIUM TUBERCULOSIS
Keywords:
A archangelica, InhA, Docking, ADME, Mycobacterium TuberculosisAbstract
Objective: Natural products have played an important role for developing new drugs and becoming popular due to toxicity and side effects of allopathic medicine. The main objective of this research work is to find drug-like inhibitor from natural compounds that can help to treat tuberculosis.
Methods: In silico docking studies were performed with four different compounds (isopimpinellin, pimpinellin, malic acid, and psoralen) from Angelica archangelica against enoyl acyl carrier protein reductase of Mycobacterium tuberculosis i.e., drug target. Flex X and Autodock Vina were used to dock the compound onto an active site of InhA to determine the probable binding of these inhibitors.
Results: Among various natural compounds that were screened as inhibitors, psoralen was found to bind in closest proximity to the InhA binding site. This is compared to the commonly recommended anti-tubercular drugs. Drug like properties of these compounds were calculated by ADME/Tox calculations.
Conclusion: According to molecular docking studies and ADME values the compound (psoralen) from Angelica archangelica was conformed as a promising lead compound and also will be the good starting point for natural plant based pharmaceutical chemistry.
Â
Downloads
References
Devi CA. Docking study on mycobacterium tuberculosis receptors AccD5 and PKS18 with selected phytochemicals. IOSR-JPBS4 2012;4:1-4.
He X, Alian A, Stroud R, Montellano PQ. Pyrrolidine carboxamides as a novel class of inhibitors of enoyl acyl carrier protein reductase. J Med Chem 2006;49(21):6308-23.
Daisy P, Nivedha RP, Bakiya RH. In silico drug designing approach for biotin protein ligase of Mycobacterium tuberculosis. AJPCR 2012;6:103-7.
Shanthi V, Ramanathan k. Identification of potential inhibitor targeting enoyl-acyl carrier protein reductase (InhA) in Mycobacterium tuberculosis: a computational approach. Springer 2013;4(3):253-61.
Planche AS, Kleandrova VV, Luan F, Cordeiro MN. In silico discovery and virtual screening of multi target inhibitors for protein in Mycobacterium tuberculosis. Comb Chem High Throughput Screening 2012;15:666-73.
Agrawal H, Kumar A, Bal NC, Siddiqi MI, Arora A. Ligand based virtual screening and biological evaluation of inhibitors of chorismate mutase (Rv1885c) from mycobacterium tuberculosis H37Rv. Bioorg Med Chem Lett 2007;17:3053-8.
Moraga ME, Njuguna NM, Mugumbate, Caballero. In silico comparison of antimycobacterial natural products with known antituberculosis drugs. J Chem Inf Model 2013;53:649-60.
Rang A, Rani S, Kumari S, Giri M. An analysis of docking study on tuberculosis inhibitors. Int J Bioinfo Res 2010;2(1):38-43.
Tomioka H, Tatano Y, Yasumoto k, Toshiaki ST. Recent advanced in antituberculardrugs. Expert Rev Respir Med 2008;2:455-71.
Luckener S, Liu N, Ende CW, Tonge P, Kisker C. A slow, tight binding inhibitor of InhA, the enoyl acyl carrier protein reductase from M ycobacterium tubercolosis. J Biochem 2010;285(19):14330-7.
Argyrou A, Jin L, Baez L, Angeletti R, John S. Proteom-wide profiling of isoniazid target in mycobacterium tuberculosis. Biochem 2006;45(47):13947-53.
Izumizono Y, Arevalo S, Koseki Y, Kuroki M, Aoki S. Identification of novel potential antibiotics for tuberculosis by in silico structure-based drug screening, Elsevier; 2011.
Hrywkiw K. InhA, Proteopedia life in 3D; 2013.
Hex, Alian A, Montellano PR. Inhibition of the Mycobacterium tuberculosis enoyl acyl carrier reductaseInhA by arylamides. Bioorg Med Chem 2007;15(21):6649-58.
Kumar UC Mahmood S. Identification of novel and potent inhibitors against InhA reductase of Mycobacterium tuberculosis through a ligand based virtual screening approach. IJPRD 2011;2(12):187-94.
Ramesh KV, Akhila BN, Deshmukh S. Molecular modelling of 2-nitropropane dioxygenase domain of Mycobacterium tuberculosis H37Rv and docking of hervalligands. Indian J Biochem Biophys 2011;48:164-9.
Jha DK, Panda L, Lavanya P, Ramaiah S, Anbarasu A. Detection and conformation of alkaloids in leaves of justice adhatoda and bioinformatics approach to elicit its antituberculosis activity. Appl Biochem Biotechnol 2012;168:980-90.
Tripathi A, Wadia N, Bindal D, Jana T. Docking studies on novel alkaloid tryptanthrin and its analogous against enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis. Indian J Biochem Biophysics 2012;49:435-41.
Vashistha RK, Nautiyal BP, Nautiyal MC. Cultivation of Angelica archangelica Linn. evaluation for economical viability at two different climatic conditions. Int J Biol Chem Sci 2008;2:563-72.
Sarkar SD, Nahar L. Natural medicine: the genus angelica. Curr Med Chem 2004;11:1479-500.
Bhat ZA, Kumar D, Shah MY. Angelica archangelica Linn. is an angel on earth for the treatment of diseases. Int J Nutr Pharmacol Neurol Dis 2011;1:36-50.
Pasqua G, Monacelli B, Silvestrini A. Accumulation of essential oils in relation to root differentiation in angelica archangelica L. Eur J Histochem 2003;47:87-90.
Barlow DJ, Buriania A, Ehrman T, Bosisiod I, Hylands PJ. In-silico studies in Chinese herbal medicines’ research: Evaluation of in-silico methodologies and phytochemical data sources, and a review of research to date. J Ethnopharmacol 2012;140:526-34.
Sathya V, Gopalakrishnan VK. In silico ADMET prediction of phytochemicals in camellia sinensis and citrus sinensis. IJPSR 2013;4:1635-7.
Choudhury A, Dey P, Sen S, Chetia P, Choudhury MD, Sharma GD. An in silico appraisal of few bioactive compounds against Kas-A for antitubercular drug efficacy. AJPCR 2011;5(1):60-2.
Choudhury A, Sen S, Dey P, Chetia P, Talukdar AD, Bhattacharjee, et al. Computational validation of 3-ammonia-3-(4-oxido-1H-imidazol-1-ium-5-yl)propane-1,1-bis (olate) as a potent anti-tubercular drug against mt-MetAP. Bioinformation 2012;8(18):875-8.