Coumarin Derivatives as Adjuvants: From In Silico Physicochemical Characterization to In Vitro Evaluation against Gram Positive Bacteria

Aims: A series of acylated coumarin derivatives have been evaluated for their in silico ADMET properties and in vitro antibacterial activities. Methods and Results: In silico analysis confirmed their physicochemical properties in conformation with various layout filters and further their ADMET properties were predicted. Antibacterial activities were evaluated by Resazurin based microbroth dilution assay against standard Gram positive bacteria: Staphylococcus aureus (MTCC No. 3160) and Bacillus cereus (MTCC No. 10085). When used alone, these derivatives showed higher MIC values. However, in combination with standard drugs they exhibited synergistic effects according to fractional inhibitory concentration index. The synergistic effect was further confirmed by time kill curves. Their cytotoxity was evaluated by haemolytic assay and they were found to be non-toxic upto a concentrations of 500 μg ml-1. Conclusion: The data support the potential use of acylated coumarin derivatives as next generation adjuvants as evaluated by their in silico ADMET analysis and in vitro antibacterial and cytotoxicity evaluation. Further research involving these combinations is warranted. Significance and Impact of the Study: This study suggests that acylated coumarin derivatives act as antibacterial adjuvants in combination with standard drugs and have potential to be used in pharmaceutical preparations.