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QSAR and docking studies on chalcone derivatives for antitubercular activity against M. tuberculosis H 37 Rv
Author(s) -
Yadav Dharmendra Kumar,
Ahmad Imran,
Shukla Aparna,
Khan Feroz,
Negi Arvind Singh,
Gupta Atul
Publication year - 2014
Publication title -
journal of chemometrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.47
H-Index - 92
eISSN - 1099-128X
pISSN - 0886-9383
DOI - 10.1002/cem.2606
Subject(s) - quantitative structure–activity relationship , chalcone , chemistry , in silico , stereochemistry , mycobacterium tuberculosis , antimycobacterial , docking (animal) , rifampicin , isoniazid , homo/lumo , biochemistry , molecule , tuberculosis , organic chemistry , antibiotics , medicine , nursing , pathology , gene
In our prior studies, we reported some known antitubercular drugs (rifampicin and streptomycin) and newly synthesized chalcone derivatives (16–26) tested in vitro against Mycobacterium tuberculosis H 37 Rv strain. Most of the tested compounds were efficient antimycobacterial agents showing minimum inhibitory concentration values ranging from 3.5 to 30 µg mL −1 . In the present work, a quantitative structure–activity relationship (QSAR) study has been performed on these active chalcone derivatives to correlate their chemical structures with their observed inhibiting activity against M. tuberculosis . A QSAR model that is able to correlate well the antitubercular activity with the chemical structures of active chalcone derivatives 16, 24, 25a, 25c, and 26 has been developed, which is potentially helpful in the design of novel and more potent antitubercular agents. The r 2 and rCV 2 of a newly derived QSAR model were 0.89 and 0.84, respectively. The QSAR study indicates that chemical properties, viz . heat of formation (kcal mol −1 ), lowest unoccupied molecular orbital energy (eV), and amine, hydroxyl, and methyl groups counts, correlate well with the activity. In silico screening results for oral bioavailability and absorption, distribution, metabolism, excretion, and toxicity compliance showed that compounds 25a, 25c, and 24 were found active similar to rifampicin and streptomycin. The docking study for the exploration of mechanism of action showed high binding affinity of active derivatives. Copyright © 2014 John Wiley & Sons, Ltd.