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Efflux pump (EP) induces resistance in mycobacteria and hence could be explored as a new target for the discovery of anti-TB agents. In search for efflux pump inhibitors from natural products, bonducellin, a homoisoflavonoid was isolated from Caesalpinia digyna roots and evaluated for modulation and EP inhibitory activity. Bonducellin showed modulation in the MIC of EtBr by eight fold at a concentration of 62.5 mg/L and also showed significant EP inhibitory activity. A synthetic scheme was designed to prepare analogues of 7-hydroxy-(E)-3-phenylmethylene-chroman-4-one by modification at the phenylmethylene-ring and the synthesized compounds were evaluated in accumulation and efflux assays. Analogues 1, 7-11, 13-15, 17 and 19 were found to be good modulators and decreased the MIC of EtBr by ≥4 fold at sub-inhibitory concentration. The compounds 8, 13 and 17 were the most potent inhibitors of ethidium bromide efflux in Mycobacterium smegmatis mc(2) 155.

The first and second line drugs used for the treatment of tuberculosis are now becoming ineffective due to emergence of resistant strains. Efflux pump provokes resistance in mycobacterium and hence could be explored as a new target for the discovery of anti-TB agents. In search of efflux pump inhibitors, MIC and modulation factor of phenylpropanoids isolated from A. galanga rhizome were determined prior to the accumulation and efflux assay. Phenylpropanoid compounds viz. 1'-S-1'-acetoxychavicol acetate, trans-p-coumaryl diacetate and 1'-S-1'-acetoxyeugenol acetate were found to be potent modulators and decreased the MIC of ethidium bromide by 64 fold at the concentration of 2.5, 6.25 and 5.0 mg/L respectively. 1'-S-1'-acetoxyeugenol acetate enhanced the accumulation and inhibited the efflux of EtBr in Mycobacterium smegmatis mc² 155 cells.