In silico docking, ADMET profiling, and bio-accessibility experimentation on Breynia retusa phytocompounds and in vitro validation for anti-proliferative potencies against ovarian carcinoma.

This study aimed to assess the medicinal properties of Breynia retusa, a plant rich in phytocompounds predominantly used as an ethnomedicinal agent in Western Ghats, which appeared to be promising for therapeutic use, especially in the treatment of ovarian cancer. Herein, its cytotoxic potential on ovarian cancer cell lines SKOV-3, neurotoxicity, antioxidant activity, and molecular docking was determined to aid in explaining the mechanisms of interactions with proteins related to ovarian cancer. B . retusa methanolic extract demonstrated exuberant antioxidant activity, with 81.91% scavenging ability of DPPH radicals and efficient reduction of phosphomolybdenum (22.98 mg ascorbic acid equivalents antioxidant capacity/g extract). The extract proved to be an important anti-inflammatory agent through membrane stabilization inhibition of 83%. The cytotoxicity study against the SKOV-3 cell line indicated an IC(50) value of 34.01 µg/mL and a very negligible neurotoxicity in SH-SY5Y cell lines. The GC-MS and HPLC profiling indicated many anticancer compounds in the extract such as secalciferol, methyl gallate, ricinoleic acid, gallic acid, and naringenin. The docking study showed significant interactions of secalciferol molecules with the key ovarian cancer proteins, which include IGF1 (-6.758 kcal/mol) and c-ERBB2 (-4.281 kcal/mol). Fatty acid derivatives and methyl gallate showed efficient dock scores (< -5.0 kcal/mol) with antioxidant (catalase and superoxide dismutase) enzymes and inflammatory cytokines (IL-6 and COX-1), respectively, as evidences of antioxidant and anti-inflammatory potentials. The bio-accessibility of phenolics and their antioxidant activity ranged above 90%, indicating the promising bioavailability of phytochemicals expected in vivo. Hence the current study emphasizes the anticancer potential of B. retusa phytocompounds that appeared to interact very strongly with ovarian cancer targets and confirms the dose-dependent cytotoxic and antioxidant activities of B. retusa methanolic extract. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-025-04276-8.