Tricyclic Sesquiterpenes From Vetiveria zizanoides (L.) Nash as Antimycobacterial Agents |
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Authors: | Gaurav R Dwivedi Shikha Gupta Sudeep Roy Komal Kalani Anirban Pal Jay P Thakur Dharmendra Saikia Ashok Sharma Nandan S Darmwal Mahendra P Darokar Santosh K Srivastava |
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Institution: | 1. Biotechnology Division, CSIR‐Central Institute of Medicinal and Aromatic Plants (Council of Scientific and Industrial Research), , Lucknow, Uttar Pradesh, 226 015 India;2. Medicinal Chemistry Division, CSIR‐Central Institute of Medicinal and Aromatic Plants (Council of Scientific and Industrial Research), , Lucknow, Uttar Pradesh, 226 015 India;3. Department of Microbiology, Dr. RML Awadh University, , Faizabad, Uttar Pradesh, India |
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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. |
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Keywords: |
ADME
antimycobacterial DNA gyrase inhibition in vivo toxicity khusenic acid khusimol
Vetiveria zizanioides
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