Anticancer Activity and Molecular Docking of Actinomycin D and Actinomycin V from Streptomyces mutabilis AL024, an Endophyte in Alpinia purpurata (Vielle.) K. Schum.

Benjamart Ruangrote, Waya Phutdhawong and Thongchai Taechowisan

Background and Objective: Actinomycins, like actinomycin D, are known anticancer agents that inhibit transcription by binding to DNA. The goal of this study was to isolate and characterize new actinomycete strains from Alpinia purpurata roots, identify their bioactive compounds and evaluate their cytotoxicity. The study further aimed to understand their mechanisms through molecular docking and predict their drug-like properties using ADMET studies. Materials and Methods: Actinomycetes were isolated from A. purpurata roots and screened for antibacterial activity. The most promising strain, AL024, was identified by morphology and 16S rRNA gene sequencing. Bioactive compounds were purified from AL024’s crude extract using TLC and their structures were determined with ESI-HRMS and NMR. The cytotoxicity of these compounds and the crude extract was assessed against various human cancer cell lines (HeLa, HepG2, MDA-MB-231) and non-cancerous Vero cells via MTT assay. Molecular docking simulated DNA binding and in silico ADMET platforms predicted pharmacokinetic and toxicological profiles. Results: Fifty-six actinomycete strains were isolated, with AL024 showing the best antibacterial activity. Identified as Streptomyces mutabilis, AL024 produced actinomycin V (compound 1) and actinomycin D (compound 2) at 1.22 and 0.96 mg/g of crude extract, respectively. Both compounds were cytotoxic to cancer cells (IC₅₀: 2.45-8.45 μg/mL) but also affected normal Vero cells (IC₅₀: 7.43-8.46 μg/mL). Docking showed both intercalate into GpC DNA, with actinomycin V exhibiting stronger binding. The ADMET predictions indicated good water solubility and Caco-2 permeability but low oral absorption and potential hepatotoxicity, though they were non-mutagenic and acutely non-toxic. Conclusion: Streptomyces mutabilis AL024 from A. purpurata is a valuable source of actinomycin V and D. These compounds show promising anticancer activity in vitro but also exhibit general cytotoxicity and predicted hepatotoxicity. Further research is essential to assess their therapeutic window and safety for drug development.

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