Crystal structure and in vitro antimicrobial activity studies of Robustic acid and other alpinumisoflavones isolated from Millettia thonningii

Abstract

We report a systematic study of the antibacterial inhibitory potential of isoflavone natural products isolated from the seeds extracts of Millettia thonningii. In an effort to gain bond topological information which may have consequences for the observed bioactivities, the crystal structure of robustic acid was solved and refined using the independent atom as well as the invariom model, and the structures were compared. Robustic acid contains a fused tricyclic unit with a benzopyran moiety, with a phenylene ring substitution on the coumarin ring similar to the alpinumisoflavones isolated from this plant. At a minimum inhibitory concentration of ~1 mg/mL, alpinumisoflavone and robustic acid were found to be cytotoxic to Staphylococcus aureus (ATCC 25923) showing a zone of inhibition (ZOI) of ~9 mm. On the other hand, at ~2 mg/mL, these compounds were found to be bacteriostatic to a hospital isolate of Salmonella typhi with about 7 mm ZOI. Taken together, these compounds offer potential new avenues for targeting both Gram positive and negative bacteria and could be useful as chemical probes for understanding these pathogens in an effort to overcome drug resistance.