Abstract
“Diversity-enhanced extracts” is an effective method of producing chemical libraries for the purpose of drug discovery. Three rare new cytochalasan derivative chaetoglobosins B1-B3 (1–3) were obtained from chemically engineered crude broth extracts of Chaetomium madrasense 375 prepared by reacting with hydrazine monohydrate and four known metabolite chaetoglobosins (4–7) were also identified from the fungus. The structures were identified by NMR and MS analysis and electronic circular dichroism simulation. In addition, the antiproliferative activities of these compounds were also evaluated, and the drug-resistant activities of cytochalasans were evaluated for the first time. Compound 6 possessed potent activity against four human cancer cells (A549, HCC827, SW620, and MDA-MB-231), and two drug-resistant HCC827 cells (Gefitinib-resistant, Osimertinib-resistant) compared with the positive controls.
Highlights
Natural products have played an important role in the development of novel drugs because of their established structural diversity (Newman and Cragg, 2016)
The macrocyclic structure of most cytochalasans contains carbonyl functional groups, which could react with hydrazine to form either hydrazones or acyl hydrazides that rarely emerge in nature
We reported several bioactive cytochalasans that were isolated from C. madrasense 375 derived from desert soil (Guo et al, 2019)
Summary
Natural products have played an important role in the development of novel drugs because of their established structural diversity (Newman and Cragg, 2016). The macrocyclic structure of most cytochalasans contains carbonyl functional groups, which could react with hydrazine to form either hydrazones or acyl hydrazides that rarely emerge in nature. This transformation could increase the nitrogen content and nucleophilic character of further reactions (Feher and Schmidt, 2003). To gain more novel cytochalasan-like bioactive compounds, a chemical transformation of crude broth extracts of C. madrasense 375 with hydrazine monohydrate was performed, followed by purification of reaction products, which offered three new cytochalasans derivatives chaetoglobosins B1-B3 (1–3), and known chaetoglobosin B (4) (Sekita et al, 1982, 1983) chaetoglobosin D (5) (Sekita et al, 1982, 1983), chaetoglobosin E (6) (Sekita et al, 1976), and cytoglobosin A (7) (Cui et al, 2010) were isolated from the unreactive raw extract of this fungus. We present the isolation, structure elucidation, bioactivities, and plausible synthesis pathways of these compounds
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