Evaluation of Newly Synthesized Schiff Base Pd(II) Complexes for Prostate Cancer Treatment Through In Vitro Cytotoxicity and Molecular Mechanistic Studies

• DOI: 10.20944/preprints202504.2221.v1
• Publication Date: 2025-04-30T01:05:33Z
• Authors: Damnjan Pantic; Nikola Mirkovic; Tatjana Vulovic; Danijela Jovanovic; Stefan Jakovljevic; Petar Canovic; Milan M Zaric; Radica Zivkovic Z...; Marina Kostic; Jovana Dragojevic; Vera Divac; Ziko Milanovic; Kristina Milisavl...; Ivanka Zelen
• Keywords: Base (topology)

Background/Objectives: Palladium(II) complexes are promising anticancer agents with potential advantages over platinum drugs. This study aimed to synthesize and characterize three novel Pd(II) (2a–c) Schiff base ligands derived from salicylic acid amine scaffolds, evaluate their antitumor activity against prostate cancer cells. Methods: The were synthesized structurally characterized. Cytotoxicity was tested on two human cell lines (PC-3, DU-145) healthy fibroblasts (MRC-5). Apoptosis induction assessed by flow cytometry focusing Bcl-2 caspase proteins. Molecular docking examined binding androgen receptor (AR) apoptotic regulators (CASP3, BCL2, BAX). DNA serum albumin (HSA) also investigated. Results: All showed significant cytotoxicity, complex 2c outperforming cisplatin (IC50: 7.1 µM in DU-145; 8.6 PC-3). confirmed as the main cytotoxic mechanism involving activation. Docking studies revealed had strongest affinity AR proteins via hydrogen bonds, π–π stacking, hydrophobic interactions. HSA supported biological relevance. Conclusions: Complex exhibits potent through apoptosis dual targeting of pathways, making it a candidate for further drug development.