Molecular docking insights into the anticancer potential of bioactive compounds from Streptomyces coelicolor KR23 through regulation of apoptotic proteins

Abstract

The biological diversity of Streptomyces, with over 500 identified species, highlights its immense potential in producing bioactive compounds with therapeutic applications, including antibacterial, antifungal, antiviral, and anticancer properties. This study focuses on the anticancer potential of Streptomyces coelicolor KR23, particularly its bioactive secondary metabolites, which exhibit cytolytic and antioxidative activities crucial for cancer treatment. Using GC-MS, bioactive compounds were identified and evaluated for their binding affinities against apoptosis-regulating proteins Bcl-2, Bax, and Bak, critical in cancer cell survival and chemotherapy resistance. Molecular docking studies using AutoDock 4 demonstrated significant binding interactions between the identified compounds, including DL-Norleucine, L-Tyrosine butyl ester, Arachidonic acid, and Oleic acid, with target proteins. The findings revealed notable binding affinities: Bcl-2 with Arachidonic acid (-6.4 KJ/mol), Bak with L-Tyrosine butyl ester (-6.1 KJ/mol), and Bax with Arachidonic acid (-5.9 KJ/mol), suggesting a high potential for therapeutic intervention. These interactions disrupt the anti-apoptotic functions of Bcl-2 and promote pro-apoptotic activities of Bax and Bak, triggering apoptosis. Additionally, the study explores the role of these compounds in modulating oxidative stress, mitochondrial membrane permeabilization, and caspase-mediated apoptosis pathways. The findings support the therapeutic versatility of Streptomyces-derived compounds in cancer therapy, addressing the challenges of drug resistance and apoptosis evasion in cancer cells. This research underscores the potential of integrating microbial metabolites with molecular docking insights for developing innovative and targeted cancer treatments.