In Silico Screening of Selected Phytochemicals for ADME Properties and Therapeutic Potential in PCOS

Abstract

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder involving multiple molecular pathways. Although several phytochemicals show potential anti-PCOS activity, their drug-likeness, ADME characteristics, toxicity, and therapeutic suitability require systematic evaluation. This study aimed to prioritize promising phytoconstituents using an integrated
in-silico approach. Materials & Methods: Selected phytoconstituents were evaluated using SwissADME, pkCSM, and OSIRIS Property Explorer. The compounds were assessed for gastrointestinal absorption, pharmacokinetic properties, Lipinski drug-likeness, Caco-2 permeability, AMES mutagenicity, toxicity risks, and overall drug score. The results were comparatively analyzed to identify
compounds with favorable pharmacokinetic and safety profiles for further investigation against PCOS-associated targets. Results & Discussion: Considerable variation was observed among the evaluated phytoconstituents. Curcumin ranked first overall, demonstrating favorable gastrointestinal absorption, ADME characteristics, Lipinski compliance, negative AMES prediction, low predicted toxicity, and a favorable drug score. Gingerol ranked second, primarily due to excellent intestinal absorption and a favorable safety profile. Catechin ranked third, showing favorable ADME and OSIRIS characteristics and the highest drug score (0.89);
however, positive AMES prediction and low Caco-2 permeability reduced its suitability. Apigenin and kaempferol showed favorable ADME profiles but were downgraded because of predicted mutagenicity. Eugenol and anethole demonstrated good absorption but comparatively higher predicted toxicity risks. Camphor exhibited the least favorable profile, with predicted mutagenicity,
tumorigenicity, irritancy, reproductive toxicity, and the lowest drug score (0.06). Conclusion: Curcumin emerged as the most promising phytoconstituent, followed by gingerol and catechin. These findings support prioritization of selected phytochemicals for further anti-PCOS investigation. However, computational predictions remain preliminary and require validation through invitro, in-vivo, pharmacological, toxicological, and mechanistic studies.