Antimicrobial and Anticancer Properties of Phenazines from Streptomyces murinus ZMA01, an Endophyte in Zea mays L.

Thongchai Taechowisan, Thanaporn Chuen-Im and Waya Phutdhawong

Background and Objective: Phenazines from Streptomyces species are known for their diverse biological activities, including antimicrobial and anticancer properties. However, purified compounds from Streptomyces murinus had not been fully characterized. This study aimed to isolate and identify phenazine-producing Streptomyces murinus ZMA01 from maize rhizosphere soil, evaluate its antimicrobial and anticancer activities, and investigate its molecular mechanisms and ADMET profiles. Materials and Methods: Streptomyces murinus ZMA01 was isolated and identified. Phenazines were extracted, purified, and tested for antimicrobial activity (MIC/MMC) against bacterial and fungal strains. Cytotoxicity IC₅₀ was assessed on Vero, HeLa, HepG2, and MDA-MB-231 cell lines. Apoptotic induction was investigated via morphological changes and Annexin V/PI staining in MDA-MB-231 cells. Molecular docking evaluated interactions with Bcl-2 family proteins. The ADMET parameters were predicted using SwissADME, PreADMET and pkCSM. Statistical analysis was conducted using SPSS (version 11.01). One-way ANOVA and Tukey’s post hoc test were employed, with significance defined as p<0.05. Results: Streptomyces murinus ZMA01 yielded 1.25 to 1.39 mg/L of phenazines. Two compounds, methyl-7-carbamoyl-phenazine-1-carboxamide and 7-hydroxyphenazine-1-carboxamide, showed selective antimicrobial activity (MICs: 32 to 256 μg/mL) and potent anticancer effects (IC₅₀: 48.63 to 148.13 μg/mL), particularly inducing apoptosis in MDA-MB-231 cells. Low toxicity to Vero cells (IC₅₀ >400 μg/mL) was noted. Molecular docking confirmed favorable binding to Bcl-2 family proteins, suggesting an apoptotic mechanism. The ADMET predictions indicated good solubility, permeability and low neurotoxicity, with potential for CYP1A2 inhibition. Conclusion: Phenazines isolated from Streptomyces murinus ZMA01 exhibit promising antimicrobial and anticancer activities with favorable ADMET profiles. These findings underscore their therapeutic potential and warrant further in vivo studies and targeted delivery optimization for treating microbial infections and cancers.

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