Investigating the bioactive compounds from Capsicum annum as a probable alternative therapy for prostate cancer treatment: a structure-based drug design approach

• Published in: Pure and applied chemistry Vol. 96; no. 5; pp. 719 - 742
• Main Authors: Abdul-Hammed, Misbaudeen, Adedotun, Ibrahim Olaide, Ismail, Ubeydat Temitope, Ayankoso, Saheed Ademola, Abdul-razaq, Roqeebah, Olajide, Monsurat, Lawal, Teslim Alabi
• Format: Journal Article
• Language: English
• Published: De Gruyter 27.05.2024
• Subjects: VCCA-2023
• ISSN: 0033-4545; 1365-3075
• DOI: 10.1515/pac-2023-1111

Prostate cancer remains a significant global health challenge, necessitating the exploration of novel therapeutic approaches. Androgen receptor (AR) signaling plays a critical role in prostate cancer progression and is a primary target for therapy. This study investigates the potential of phytochemicals from (Bell pepper) along with two common standand drugs (Apalutamide and Enzalutamide) as inhibitors of the human androgen receptor (AR) and prostate-specific membrane antigen (PSMA). Utilizing computer-aided drug design techniques, molecular docking studies were conducted to evaluate the binding affinities of selected ligands against AR (PDB ID: 1XOW) and PSMA (PDB ID: 2XEI), their ADMET properties, drug-likeness, oral bioavailability, and bioactivity profiles were also examined. Coumaroylquinic acid and 5-O-caffeoylquinic acid methyl-ester emerged as top-performing ligands, demonstrating strong binding affinities of −9.4 kcal/mol and −9.2 kcal/mol, respectively, against PSMA. Additionally, molecular dynamics simulations provided insights into the stability of protein-ligand complexes, with Coumaroylquinic acid exhibiting a stable binding conformation throughout the simulation. These findings suggest the potential of phytochemicals, particularly Coumaroylquinic acid and 5-O-caffeoylquinic acid methyl-ester, as promising inhibitors of PSMA. Moreover, other ligands (Caffeoylglucoside and 1-O-galloyl-beta- -glucose) identified in the study demonstrate interactions with AR, highlighting a multifaceted approach to prostate cancer treatment. Overall, this study underscores the potential of phytochemicals as a source of novel therapeutic agents for prostate cancer, laying the groundwork for further lead optimization efforts.