Abstract 5342: Assessment of polyphenolic secondary metabolites and small molecules against the xenobiotic metabolic and cell cycle regulatory proteins in prostate cancer

Abstract Background: Prostate cancer (PCa) is the second most frequent kind of cancer in males globally after Lung Cancer. In clinical practice, medicines that act as antagonists/partial agonists of hormone receptors against prostate tissue are employed in PCa treatment. Cyproterone acetate, Flutamide, and Bicalutamide are prominent medications that induce acute and long-term toxicity and create drug resistance in patients and remission. We concentrated on flavonoids since they are non-cytotoxic and have substantial showing inhibitory action. Methodology: We selected 560 flavonoids and small compounds along with 3 targets from the extensive literature review. Three-dimensional (3D) structures of selected proteins were obtained from Protein Data Bank, docked with 560 flavonoids and small molecules 3D structures, obtained from PubChem and CHEMBL database using Gold Docking Software. ADME characteristics were used to determine their bioactivities in the human body and drug-like investigations by using SwissADME and Zinc database, while Lipinski's rule of five was used to evaluate the flavonoids' anti-prostate cancer efficacy. Additionally, we have performed molecular simulation at 100ns and furthermore, we will perform cytotoxicity analysis. Results: Diosmetin (58.72), Lapatinib Ditosylate (121.61), and Estramustine Phosphate Sodium (143.38) has the highest binding affinity for CDKN2 (4EK3), CYP17A1(3RUK), and CYP19A1(3S79), respectively, and are stable throughout 100ns simulation studies. At present, we are working on cytotoxicity studies on PC3 cell lines. As per the literature review by Ansar et al. 2022 quercetin and thymoquinone induce cytotoxicity in breast, lung, and prostate cancer cells effectively; MCF-7 cells were the most sensitive cells to quercetin with an IC50 value of 50 μM and PC3 cells were more sensitive to thymoquinone with an IC50 value of 20 μM. Conclusion: As a result of our findings, these four Flavonoids may be viable candidates for additional research into PCa prevention or management.Keywords: Diosmetin, Lapatinib Ditosylatye, Prostate cancer, In-silico, Simulation Citation Format: Sumit Sheoran, Swati Arora, Tanmay Basu, Naidu Subbarao, Atul Kumar Upadhyay, Sugunakar Vuree. Assessment of polyphenolic secondary metabolites and small molecules against the xenobiotic metabolic and cell cycle regulatory proteins in prostate cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5342.