Guo Qingfeng, Chen Jinhua, Ren Yuwei, Yin Zhenhua, Zhang Juanjuan, Yang Baocheng, Wang Xuewei, Yin Wenbing, Zhang Wancun, Ding Gang, Chen Lin
Zhengzhou Key Laboratory of Synthetic Biology of Natural Products, Zhengzhou Key Laboratory of Medicinal Resources Research, Comprehensive Utilization of Edible and Medicinal Plant Resources Engineering Technology Research Center, Huanghe Science and Technology College, Zhengzhou, China.
Department of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Front Chem. 2021 Apr 21;9:620589. doi: 10.3389/fchem.2021.620589. eCollection 2021.
"Diversity-enhanced extracts" is an effective method of producing chemical libraries for the purpose of drug discovery. Three rare new cytochalasan derivative chaetoglobosins B-B (-) were obtained from chemically engineered crude broth extracts of 375 prepared by reacting with hydrazine monohydrate and four known metabolite chaetoglobosins () 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 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.
“多样性增强提取物”是一种为药物发现目的而生产化学文库的有效方法。通过与水合肼反应制备的375种化学工程粗肉汤提取物中获得了三种罕见的新细胞松弛素衍生物球毛壳菌素B - B（-），并且还从该真菌中鉴定出了四种已知的代谢产物球毛壳菌素（）。通过核磁共振（NMR）、质谱（MS）分析和电子圆二色性模拟确定了其结构。此外，还评估了这些化合物的抗增殖活性，并首次评估了细胞松弛素的耐药活性。与阳性对照相比，化合物对四种人类癌细胞（A549、HCC827、SW620和MDA - MB - 231）以及两种耐药HCC827细胞（吉非替尼耐药、奥希替尼耐药）具有强效活性。
