Synergy Potential of Indole Alkaloids and Its Derivative against Drug‐resistant Escherichia coli |
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| Authors: | Gaurav Raj Dwivedi Shikha Gupta Anupam Maurya Shubhandra Tripathi Ashok Sharma Mahendra P Darokar Santosh K Srivastava |
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| Institution: | 1. Biotechnology Division, Central Institute of Medicinal and Aromatic Plants (CSIR‐CIMAP), Lucknow, India;2. School of Environmental Sciences, Babasaheb Bhimrao Ambedkar Central University, Lucknow, India;3. Medicinal Chemistry Department, Central Institute of Medicinal and Aromatic Plants (CSIR‐CIMAP), Lucknow, India |
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| Abstract: | Antibacterial and synergy potential of naturally occurring indole alkaloids (IA): 10‐methoxy tetrahydroalstonine ( 1 ), isoreserpiline ( 2 ), 10 and 11 demethoxyreserpiline ( 3 ), reserpiline ( 4 ), serpentine ( 5 ), ajmaline ( 6 ), ajmalicine ( 7 ), yohimbine ( 8 ), and α ‐yohimbine ( 9 ) was evaluated using microbroth dilution assay. Further, α ‐yohimbine ( 9 ) was chemically transformed into six semisynthetic derivatives ( 9A‐9F ), and their antibacterial and synergy potential in combination with nalidixic acid (NAL) against E. coli strains CA8000 and DH5α were also evaluated. The IA 1 , 2 , 4 , 5 , 9 and the derivative 9F showed eightfold reduction in the MIC of NAL against the DH5 α and four‐ to eightfold reduction against CA8000. These alkaloids also reduced MIC of another antibiotic, tetracycline up to 8folds, against the MDREC‐KG4, a multidrug‐resistant clinical isolate of E. coli. Mode of action study of these alkaloids showed efflux pumps inhibitory potential, which was supported by their in silico binding affinity and downregulation of efflux pump genes. These results may be of great help in the development of cost‐effective antibacterial combinations for treating patients infected with multidrug‐resistant Gram‐negative infections. |
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| Keywords: | antibacterial combination indole alkaloids
MDREC
nalidixic acid semisynthetic derivatives tetracycline |
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