Dwivedi GR, Gupta S, Roy S, Kalani K, Pal A, Thakur JP, Saikia D, Sharma A, Darmwal NS, Darokar MP, Srivastava SK
Chemical Biology & Drug Design, 2013
ABSTRACT:
Two bioactive constituents, khusenic acid (1) and khusimol (2), were isolated and characterized from hexane fraction of Vetiveria zizanoides roots. Compounds, 1 and 2, were tested against the various drug-resistant mutants of Mycobacterium smegmatis. The results showed that compound 1 was 4 times more active than the standard drugs ciprofloxacin (CF) and nalidixic acid (NA) against the ciprofloxacin (CSC 101) and lomefloxacin(LOMR5)-resistant mutants, whereas the compound 2 was 2 times more active against the CSC 101 than the NA and CF. Further, these compounds were tested against the virulent strain H37Rv of Mycobacterium tuberculosis, which showed that 1 was two times more active than NA, while 2 was equally active to NA. In in silico docking study, 1 showed better binding affinity than 2 with both subunits of the bacterial DNA gyrase, which was further confirmed from the in vitro bacterial DNA gyrase inhibition study. The in silico ADME analysis of 1 and 2 showed better intestinal absorption, aqueous solubility and ability to penetrate blood-brain barrier. Finally, compound 2 was found safe at the highest dose of 2000 mg/kg body weight. Being edible, fragrant natural products, 1 and 2 will have advantage over the existing synthetic drugs.
CITATION:
Dwivedi GR, Gupta S, Roy S, et al. Tricyclic Sesquiterpenes From Vetiveria zizanoides (L.) Nash as Antimycobacterial Agents. Chem Biol Drug Des. 2013;82(5):587-594.
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