2026-10-12T11:16:31Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33952342 2026-09-21T11:55:28Z category_388 portal_316 item_type_3 month_year_09_2026

Data Sheet 1_Preclinical identification of an oxadiazole-pyrazole lead targeting prostate cancer through integrated mechanistic evaluation.pdf Vanktesh Kumar (25083250) Pankaj Wadhwa (25083253) Shubham Kumar (9308774) Oncology and Carcinogenesis not elsewhere classified androgen receptor cytotoxicity molecular docking oxadiazole prostate cancer pyrazole reactive oxygen species Background<p>Prostate cancer remains a major cause of cancer-related mortality among men, while resistance to androgen deprivation therapy emphasizes the need for new therapeutic strategies. Molecular hybridization of pharmacologically relevant heterocycles offers a rational approach for developing novel anticancer agents.</p>Methods<p>Twenty oxadiazole–pyrazole hybrids (VS-01–VS-20) were designed, synthesized, and evaluated using molecular docking against the androgen receptor (PDB ID: 1Z95), followed by in vitro antiproliferative assessment against androgen-dependent LNCaP and androgen-independent PC-3 prostate cancer cells. The lead compound was further investigated for its effects on androgen receptor expression, intracellular reactive oxygen species (ROS), cell-cycle progression, and apoptosis using flow cytometry and fluorescence microscopy. ADMET properties were additionally predicted computationally.</p>Results<p>VS-04 demonstrated a favorable interaction profile within the androgen receptor ligand-binding pocket and exhibited potent antiproliferative activity, with IC₅₀ values of 394.95 ± 3.03 nM against PC-3 and 464.85 ± 4.29 nM against LNCaP cells. Docking–activity correlation analysis revealed a moderate and significant association between docking affinity and PC-3 antiproliferative activity, whereas no significant correlation was observed for LNCaP cells. VS-04 treatment produced a concentration-dependent reduction in androgen receptor expression and increased intracellular ROS levels. Mechanistic studies further demonstrated pronounced S-phase accumulation and induction of apoptosis, with the total apoptotic population increasing from 7.45% in control cells to 47.83% following VS-04 treatment.</p>Conclusion<p>The integrated computational and experimental evaluation identified VS-04 as a promising oxadiazole–pyrazole lead with potent antiproliferative activity against prostate cancer cells. Its activity was associated with AR modulation, oxidative stress, cell-cycle perturbation, and apoptotic cell death, supporting further structural optimization and preclinical investigation of this scaffold for prostate cancer therapy.</p> 2026-09-21T11:55:28Z Dataset Dataset 10.3389/fonc.2026.1953079.s001 https://figshare.com/articles/dataset/Data_Sheet_1_Preclinical_identification_of_an_oxadiazole-pyrazole_lead_targeting_prostate_cancer_through_integrated_mechanistic_evaluation_pdf/33952342 CC BY 4.0