QSAR and docking studies on chalcone derivatives for antitubercular activity against M.tuberculosis H37Rv

Abstract

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 H37Rv strain. Most of the tested compounds were efficient antimycobacterial agents showing minimum inhibitory concentration values ranging from 3.5 to 30μgmL-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 r2 and rCV2 of a newly derived QSAR model were 0.89 and 0.84, respectively. The QSAR study indicates that chemical properties, viz. heat of formation (kcalmol-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. In our prior studies, we reported newly synthesized chalcone derivatives (16-26) tested in vitro against Mycobacterium tuberculosis H37Rv. 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, quantitative structure-activity relationship and docking studies on active chalcone derivatives were performed to correlate structures with observed inhibiting activity. In silico screening results for oral bioavailability and absorption, distribution, metabolism, excretion, and toxicity showed that compounds 25a, 25c, and 24 were active similar to rifampicin and streptomycin. © 2014 John Wiley & Sons, Ltd.