Abstract
In the present work, a ligand-based 3D pharmacophore and QSAR approach is used for the selection of potentially active compounds for inhibitory action against the enoyl-ACP-reductase (InhA) from Mycobacterium tuberculosis, followed by molecular modelling, dynamic simulation and binding energy calculation methods. The biological activity of the molecules is measured by logIC50 (50% inhibitory concentration). The molecular descriptors are used to build statistical models to predict the biological activity of interest.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
D.A. Rozwarski, Crystal structure of the Micobacterium tuberculosis enoyl-ACP reductase, InhA in complex with NAD+ and a C16 fatty acyl substrate. J. Biol. Chem. 274, 15582–155589 (1999)
S.R. Luckner, X ray crystal structure of a slow, tight binding inhibitor of InhA from M. Tb. J. Biol. Chem. 285, 14330 (2010)
X. He et al., Pyrrolidine carboxamides as a novel class of inhibitors of InhA from M. Tb. J. Med. Chem. 49(21), 6308–6323 (2006)
A. Punkvang et al., Investigating the structural basis of arylamides to improve potency against M. Tuberculosis strain through molecular dynamics simulation. Eur. J. Med. Chem. 45, 5585–5593 (2010)
Schroeder et al, Molecular dynamics simulation studies of the wild type I 21V and I 16T mutants of isoniazid resistant M. Tb InhA in complex with NADH, towards understanding of NADH–InhA different affinities. Biophy. J. 89, 876–884 (2005)
X. He et al., Inhibition of the MTb enoyl acyl carrier protein reductase InhA by arylamides. Bioorg. Med. Chem. 15(21), 6649–6658 (2007)
G. Subba Rao, R. Vijayakrishnan, M. Kumar, Structure based design of a novel class of potent inhibitors of InhA, the enoyl acyl carrier protein reductase from Micobacterium tuberculosis: A computer modeling approach. Chem. Biol. Drug Des. 72, 444–449 (2008)
M. Kumar, R. Vijayakrishnan, G. Subba Rao, In silico structure-based design of a novel class of potent and selective small peptide inhibitor of M. Tb. Dihydrate reductase, a potential target for anti TB. drug discovery. Mol. Divers. 14(3), 594–604 (2010)
A. F. Kouassi et al., Computer-aided design of orally bioavailable pyrrolidine carboxamide inhibitors of enoyl-acyl carrier protein reductase of Mycobacterium tuberculosis with favorable pharmacokinetic profiles. Int. J. Mol. Sci. 16, 29744–29771 (2015)
J. Muralidharan, K. Suguna, N. Surolia, Exploring the interaction energies for the binding of hydroxydiphenyl ethers to enoyl acyl carrier protein reductases. J. Biomol. Struct. Dyn. 20, 589–594 (2003)
S.G. Kini, A.K. Bhat, Synthesis, antitubercular activity and docking study of novel cyclic azole substituted diphenyl ether derivatives. Eur J. Med. Chem. 44, 492–500 (2009)
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Singapore Pte Ltd.
About this paper
Cite this paper
Sarkar, I., Goswami, S., Majumder, P. (2020). To Explore Compounds as Tuberculosis Inhibitors—A Combination of Pharmacophore Modelling, Virtual Screening and Molecular Docking Studies. In: Maharatna, K., Kanjilal, M., Konar, S., Nandi, S., Das, K. (eds) Computational Advancement in Communication Circuits and Systems. Lecture Notes in Electrical Engineering, vol 575. Springer, Singapore. https://doi.org/10.1007/978-981-13-8687-9_33
Download citation
DOI: https://doi.org/10.1007/978-981-13-8687-9_33
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-8686-2
Online ISBN: 978-981-13-8687-9
eBook Packages: EngineeringEngineering (R0)