New Metabolites and Bioactive Actinomycins from Marine-Derived Streptomyces sp. ZZ338

Abstract

An extract prepared from the culture of a marine-derived actinomycete Streptomyces sp. ZZ338 was found to have significant antimicrobial and antiproliferative activities. A chemical investigation of this active extract resulted in the isolation of three known bioactive actinomycins (1–3) and two new metabolites (4 and 5). The structures of the isolated compounds were identified as actinomycins D (1), V (2), X0β (3), 2-acetylamino-3-hydroxyl-4-methyl-benzoic acid methyl ester (4), and N-1S-(4-methylaminophenylmethyl)-2-oxo-propyl acetamide (5) based on their nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectroscopy (HRESIMS) data as well as their optical rotation. This class of new compound 5 had never before been found from a natural resource. Three known actinomycins showed activities in inhibiting the proliferation of glioma cells and the growth of methicillin-resistant Staphylococcus aureus, Escherichia coli, and Candida albicans and are responsible for the activity of the crude extract. Actinomycin D (1) was also found to downregulate several glioma metabolic enzymes of glycolysis, glutaminolysis, and lipogenesis, suggesting that targeting multiple tumor metabolic regulators might be a new anti-glioma mechanism of actinomycin D. This is the first report of such a possible mechanism for the class of actinomycins.

Anti-glioma Natural Products Downregulating Tumor Glycolytic Enzymes from Marine Actinomycete Streptomyces sp. ZZ406

“…Our previous studies 23 , 27 , 28 proposed that the in vitro SRB screening assay combined with the detection of lactate production might be a new way to discover novel anti-glioma compounds from marine actinomycetes with unique mechanism by regulating multiple tumor metabolic enzymes. The data from this study further support this proposal.…”

“…Each extract prepared from the cultures of the isolate marine bacteria was assayed by sulforhodamine B (SRB) method for its activities in inhibiting the proliferation of glioma cells and in reducing the production of lactate in glioma cells. It has been found that several extracts had antiproliferative activity and also reduced lactate production in glioma cells, resulting in the discovery of several anti-glioma compounds by downregulating multiple tumor glycolytic enzymes 23 , 27 , 28 . These results suggested that the in vitro antiproliferative active assay in combination with the determination of lactate production might be a new method to discover novel anti-glioma agents with the unique mechanism of targeting multiple tumor metabolic regulators.…”

Actinobacteria from Antarctica as a source for anticancer discovery

“…They are a family of bicyclic chromopeptide lactones that attach two pentapeptide lactones of nonribosomal origin. Its use dates approximately 70 years ago, acting under several types of malignant human tumours, including nephroblastoma (Wilms’ tumour) and childhood rhabdomyosarcoma 67 – 69 , and has attracted attention for its potential to assist in the development growth of multi-drug resistance strains and inhibition of HIV-1 reverse transcriptase 44 , 70 , 71 .…”

Involvement of Reactive Oxygen Species in the Hepatorenal Toxicity of Actinomycin V In Vitro and In Vivo

“…Actinomycin V (Act V), which is also extracted from the marine-derived actinomycete Streptomyces sp. [ 1 ], has a similar structure to that of Act D ( Figure 1 ). In our previous studies [ 10 , 11 ], Act V was found to be more cytotoxic to tumor cells than Act D. Moreover, Act V inhibited the migration and metastasis of breast cancer cells.…”

“…Actinomycin D (Act D), extracted and separated from the marine-derived actinomycete Streptomyces sp . [ 1 ], is a chemotherapy medication that inhibits RNA synthesis [ 2 ]. It has been used for the treatment of multiple cancer types, including Wilms tumor [ 3 ], rhabdomyosarcoma [ 4 ], Ewing’s sarcoma [ 5 ], trophoblastic neoplasms [ 6 ] and certain types of ovarian cancer [ 7 ].…”