Tricyclic Sesquiterpenes From Vetiveria zizanoides ( L.) Nash as Antimycobacterial Agents.

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 M ycobacterium 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. [ABSTRACT FROM AUTHOR]