Journal
CHEMICAL BIOLOGY & DRUG DESIGN
Volume 82, Issue 5, Pages 587-594Publisher
WILEY
DOI: 10.1111/cbdd.12188
Keywords
ADME; antimycobacterial; DNA gyrase inhibition; in vivo toxicity; khusenic acid; khusimol; Vetiveria zizanioides
Funding
- CSIR Network project [BSC 0203]
- CSIR
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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 2000mg/kg body weight. Being edible, fragrant natural products, 1 and 2 will have advantage over the existing synthetic drugs.
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