Synthesis, Characterization Anti-Prostate Cancer Activity and Molecular Docking of New Succinimide Derivatives

Abstract

Prostate cancer is a leading cause of mortality among men worldwide and is a disease characterized by genetic and epidemiological heterogeneity. Androgen receptors play a pivotal role in the pathogenesis and progression of prostate cancer to its aggressive form. Studies indicate that combining chemotherapy with androgen receptor-targeted therapy improves patient survival, prompting organic chemists to develop novel, effective agents against prostate cancer. In this study, a series of succinimide derivatives were synthesized and characterized using mass spectrometry, ¹H-NMR, ¹³C-NMR, and FT-IR. Their biological activity against castration-resistant prostate cancer (PC-3 cells) was evaluated using the MTT assay. Based on IC50 values, several synthesized compounds (C₂, C₅, F₄, R₂) demonstrated anti-prostate cancer activity; notably, compounds C₅, C₂, and F₄ exhibited the highest cytotoxicity (IC50 values ​​of 39, 46, and 49 µg/mL, respectively). Additionally, molecular docking simulations were performed using the MOE software (2024 version) to investigate the binding affinity and mode of interaction within the active site of the AKT1 protein. However, this class of compounds requires further study to optimize various properties and ultimately develop effective treatments for androgen-independent prostate cancer