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Tricyclic Sesquiterpenes From V etiveria zizanoides ( L .) Nash as Antimycobacterial Agents
Author(s) -
Dwivedi Gaurav R.,
Gupta Shikha,
Roy Sudeep,
Kalani Komal,
Pal Anirban,
Thakur Jay P.,
Saikia Dharmendra,
Sharma Ashok,
Darmwal Nandan S.,
Darokar Mahendra P.,
Srivastava Santosh K.
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12188
Subject(s) - chemistry , dna gyrase , antimycobacterial , nalidixic acid , adme , ciprofloxacin , mycobacterium smegmatis , mycobacterium tuberculosis , stereochemistry , biochemistry , escherichia coli , in vitro , antibiotics , pathology , gene , medicine , tuberculosis
Two bioactive constituents, khusenic acid ( 1 ) and khusimol ( 2 ), were isolated and characterized from hexane fraction of V etiveria zizanoides roots. Compounds, 1 and 2 , were tested against the various drug‐resistant mutants of M ycobacterium 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( LOMR 5)‐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.