title: Tricyclic sesquiterpenes from Vetiveria zizanoides (L.) Nash as antimycobacterial agents.
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.
authors.affiliation: Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants (Council of Scientific and Industrial Research), P.O. CIMAP, Lucknow, Uttar Pradesh, 226 015, India.
authors.forename: Gaurav R
authors.initials: GR
authors.lastname: Dwivedi
authors.forename: Shikha
authors.initials: S
authors.lastname: Gupta
authors.forename: Sudeep
authors.initials: S
authors.lastname: Roy
authors.forename: Komal
authors.initials: K
authors.lastname: Kalani
authors.forename: Anirban
authors.initials: A
authors.lastname: Pal
authors.forename: Jay P
authors.initials: JP
authors.lastname: Thakur
authors.forename: Dharmendra
authors.initials: D
authors.lastname: Saikia
authors.forename: Ashok
authors.initials: A
authors.lastname: Sharma
authors.forename: Nandan S
authors.initials: NS
authors.lastname: Darmwal
authors.forename: Mahendra P
authors.initials: MP
authors.lastname: Darokar
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D001665:Binding Sites; D049930:Chrysopogon / Q000737:chemistry* / Q000378:metabolism; D027081:DNA Gyrase / Q000737:chemistry / Q000378:metabolism; D005260:Female; D051379:Mice; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D020102:Mycobacterium smegmatis / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D018517:Plant Roots / Q000737:chemistry / Q000378:metabolism; D000081223:Polycyclic Sesquiterpenes; D017434:Protein Structure, Tertiary; D012717:Sesquiterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018675:Toxicity Tests
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; D059005:Topoisomerase II Inhibitors; C091305:khusimol; C588286:khusenic acid; D027081:DNA Gyrase
keywords: ADME; DNA gyrase inhibition; Vetiveria zizanioides; antimycobacterial; in vivo toxicity; khusenic acid; khusimol