Hydrazine-Containing Heterocycle Cytochalasan Derivatives From Hydrazinolysis of Extracts of a Desert Soil-Derived Fungus Chaetomium madrasense 375

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.

Chaetoglobosin E inhibits tumor growth and promotes the anti-tumor efficacy of cytotoxic drugs in esophageal squamous cell carcinoma by targeting PLK1

“…Previous reports have demonstrated that there is a transition between cell apoptosis and pyroptosis in cancer ( 12 , 13 ). The present study indicated that chaetoglobosin E induced cell apoptosis; thus, we further explored whether chaetoglobosin E affected pyroptosis.…”

“…They exert a broad range of biological activities, among which their antitumor activity has been studied most extensively (10). Previously, we reported the anti-tumor activities of a series of chaetoglobosins isolated from the metabolites of Chaetomium madrasense 375 (11)(12)(13). We found that chaetoglobosin E had a more potent anti-tumor effect against A549, HCC827, SW620, and MDA-MB-231 cells compared to those of chaetoglobosin B1, B2, B3, B, D, cytoglobosin A, and cisplatin (12).…”

“…Previously, we reported the anti-tumor activities of a series of chaetoglobosins isolated from the metabolites of Chaetomium madrasense 375 (11)(12)(13). We found that chaetoglobosin E had a more potent anti-tumor effect against A549, HCC827, SW620, and MDA-MB-231 cells compared to those of chaetoglobosin B1, B2, B3, B, D, cytoglobosin A, and cisplatin (12). Moreover, several studies also have demonstrated that chaetoglobosin E, which is extracted from Chaetomium globosum, exerts anti-tumor activity against HeLa, HCT-116, and KB cells (14)(15)(16).…”

Development of Indole Alkaloid-Type Dual Immune Checkpoint Inhibitors Against CTLA-4 and PD-L1 Based on Diversity-Enhanced Extracts

“…Diversity-enhanced extracts are obtained from multiple chemical reactions that directly form new carbon–carbon bonds in the extracts of natural resources in order to afford diverse natural product–like library-bearing remodeled molecular scaffolds. Several chemical transformations of natural extracts using similar methods have been reported ( López et al, 2007 ; Ramallo et al, 2011 ; Ramallo et al, 2018 ; Solís et al, 2019 ; Salazar et al, 2020 ) ( Kawamura et al, 2011 ; Kamauchi et al, 2015 ; Tomohara et al, 2016 ; Kamauchi et al, 2018 ; Guo et al, 2021 ; Sulistyowaty et al, 2021 ), but most of the methods simply provide compounds in which some functional groups have been transformed. However, we have defined diversity-oriented extracts as those natural extracts formed by reactions that produce multiple diversities similar to that observed in diversity-oriented synthesis, including the formation of new carbon–carbon bonds, modification of molecular scaffolds ( Oshima and Kikuchi, 2018 ), and conversion of functional groups.…”

DataSheet1.PDF

“…Several chemical transformations of natural extracts using similar methods have been reported (López et al, 2007;Ramallo et al, 2011;Ramallo et al, 2018;Solís et al, 2019;Salazar et al, 2020) (Kawamura et al, 2011;Kamauchi et al, 2015;Tomohara et al, 2016;Kamauchi et al, 2018;Guo et al, 2021;Sulistyowaty et al, 2021), but most of the methods simply provide compounds in which some functional groups have been transformed. However, we have defined diversity-oriented extracts as those natural extracts formed by reactions that produce multiple diversities similar to that observed in diversity-oriented synthesis, including the formation of new carbon-carbon bonds, modification of molecular scaffolds (Oshima and Kikuchi, 2018), and conversion of functional groups.…”