Isolation, Docking and In Silico ADME-T Studies of Acacianol: Novel Antibacterial Isoflavone Analogue Isolated from Acacia leucophloea Bark

Background: The plant Acacia leucophloea (Roxb.) Willd. of the family Fabaceae is of paramount importance in Indian medicine. Objectives: We sought to evaluate the in vitro anti-microbial activity of A. leucophloea stem bark extract together with its phytochemical characterization and exploration of drug-likeness attributes. Methods: In vitro Kirby-Bauer disc-diffusion and tube-dilution assays were exploited for determining the anti-microbial activity of the methanolic bark extracts against several bacterial test strains. Spectral characterization of the isolated phytoconstituents was performed using spectroscopy techniques viz., UV, IR, 1H NMR, and mass spectroscopy followed by the in silico studies like docking and ADME-T studies. Results: The crude methanolic extracts were active against all the bacterial test strains, albeit weakly or moderately, as indicated by the zone of inhibition and minimum inhibitory concentration in the anti-microbial assays. The isolated phytoconstituent was identified to be 3-(3,4-dihydro-5-methoxy-2H-chromen-6-yl)-2,5dimethoxy-2H-chromen-7-ol (hereby coined as acacianol), a novel isoflavone analog. Acacianol demonstrated a strong binding affinity towards the bacterial DNA gyrase over clorobiocin, especially in the case of cavity 4 with no predicted toxicities in silico, except skin sensitization and chromosome damage.

Automated summary

The research showed that the crude methanolic extracts of Acacia leucophloea stem bark exhibited antimicrobial activity against all tested bacterial strains, albeit weak or moderate. A novel isoflavone analog, named acacianol, was identified in the study with a strong binding affinity towards bacterial DNA gyrase. In silico studies indicated no predicted toxicities except for skin sensitization and chromosome damage.