Streptomyces griseus KJ623766: A Natural Producer of Two Anthracycline Cytotoxic Metabolites β- and γ-Rhodomycinone.

Ahmed S Abu Zaid,Mahmoud A Yassien,Ahmed E Aleissawy,Khaled M Aboshanab,Ibrahim S Yahia,Nadia A Hassouna

doi:10.3390/molecules26134009

Ahmed S Abu Zaid, Mahmoud A Yassien + Show 4 more

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https://doi.org/10.3390/molecules26134009

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Abstract

Background: This study aimed to produce, purify, structurally elucidate, and explore the biological activities of metabolites produced by Streptomyces (S.) griseus isolate KJ623766, a recovered soil bacterium previously screened in our lab that showed promising cytotoxic activities against various cancer cell lines. Methods: Production of cytotoxic metabolites from S. griseus isolate KJ623766 was carried out in a 14L laboratory fermenter under specified optimum conditions. Using a 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium-bromide assay, the cytotoxic activity of the ethyl acetate extract against Caco2 and Hela cancer cell lines was determined. Bioassay-guided fractionation of the ethyl acetate extract using different chromatographic techniques was used for cytotoxic metabolite purification. Chemical structures of the purified metabolites were identified using mass, 1D, and 2D NMR spectroscopic analysis. Results: Bioassay-guided fractionation of the ethyl acetate extract led to the purification of two cytotoxic metabolites, R1 and R2, of reproducible amounts of 5 and 1.5 mg/L, respectively. The structures of R1 and R2 metabolites were identified as β- and γ-rhodomycinone with CD50 of 6.3, 9.45, 64.8 and 9.11, 9.35, 67.3 µg/mL against Caco2, Hela and Vero cell lines, respectively. Values were comparable to those of the positive control doxorubicin. Conclusions: This is the first report about the production of β- and γ-rhodomycinone, two important scaffolds for synthesis of anticancer drugs, from S. griseus.

Highlights

Worldwide cancer incidence and mortality have always been a concern to the community
The results showed that the Cell Free Culture Supernatant (CFCS) ethyl acetate extract has potential cytotoxic activities against both cell lines with higher activity against Caco2 (CD50 14 μg/mL) than Hela cell line (CD50 20 μg/mL), which indicates the presence of metabolites with higher selectivity to human colorectal adenocarcinoma (Table 1)
Natural products are likely to provide many of the lead structures, and these will be used as templates for the construction of novel compounds with enhanced biological properties, so natural products have been the mainstay of cancer chemotherapy for the past 30 years [6]

Summary

Introduction

Worldwide cancer incidence and mortality have always been a concern to the community. The cancer mortality rate has generally declined over the years; there is still an increased mortality rate in poorer countries that receives considerable attention from healthcare professionals [1]. This suggests the importance of prompt detection, effective treatment, and successful prevention strategies [1]. Microbial metabolites, have been the mainstay of cancer chemotherapy These products could provide many of the lead structures that can be used for production of new derivatives with improved biological activities [2]. Results: Bioassay-guided fractionation of the ethyl acetate extract led to the purification of two cytotoxic metabolites, R1 and R2, of reproducible amounts of 5 and 1.5 mg/L, respectively. Values were comparable to those of the positive control doxorubicin

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