Multitarget Ensemble Docking of Potent Anticancer and Antioxidant Active Compounds from the Acacia auriculiformis and Acacia crassicarpa

Bioactive chemicals derived from Acacia auriculiformis and A. crassicarpa have the potential to be developed as sources of anti-cancer raw materials and antioxidants, given that these plants are fast-growing species with medicinal capability. The in silico method was successful in identifying these bioactive chemicals for the preliminary study. Using an in silico approach, this work aimed to identify the most potent compounds as inhibitors of six cancer and stress oxidative therapy-targeted proteins from these two distinct Acacia species. Seventeen out of the 37 compounds examined exhibited low affinity and satisfied the drug-likeness criterion. Five active chemicals were identified by redocking analysis: auriculoside, 3-(3,4-dihydroxybenzyl)-7-hydroxychroman-4-one, kaempferol 7-O-glucoside, quercetin 7-O-glucoside, and keto-teracacidin. According to simulations of molecular dynamics, molecular motion occurs with a root mean square deviation of less than four and generates at least eleven receptor conformations for 0 to 100 ns. Auriculoside showed the lowest average binding energy against four receptors in colorectal and breast cancer, as determined by ensemble docking, followed by 3-(3,4-dihydroxybenzyl)-7-hydroxychroman-4-one, quercetin 7-O-glucoside, and kaempferol 7-O-glucoside. Auriculoside shown multitarget inhibitory effect against colorectal cancer by inhibiting cyclin dependent kinase-6 and breast cancer by inhibiting epidermal growth factor receptor and mammalian target of rapamycin. Auriculoside has the powerful ability to inhibit glycogen synthase kinase-3 beta, hence regulating oxidative stress. Kaempferol 7-O-glucoside and quercetin 7-O-glucoside also exhibited a possible single protein targeting method against breast cancer. These findings are essential for future research targeted at developing these plants as potent natural therapeutic raw materials and for isolating or synthesizing compounds with anticancer and oxidative stress-regulating antioxidant properties.