title: Epicochalasines A and B: Two Bioactive Merocytochalasans Bearing Caged Epicoccine Dimer Units from Aspergillus flavipes.
abstract: Two bioactive merocytochalasans, epicochalasines A (1) and B (2), a new class of cytochalasans bearing unexpected scaffolds consisting of fused aspochalasin and epicoccine dimer moieties, were isolated from the liquid culture broth of Aspergillus flavipes. Both 1 and 2 possess a hendecacyclic 5/6/11/5/6/5/6/5/6/6/5 ring system containing an adamantyl cage and as many as 19 stereogenic centers; however, the fusion patterns of 1 and 2 differ greatly, thus resulting in different carbon skeletons. The absolute configurations of 1 and 2 were determined by X-ray diffraction and calculated ECD, respectively. The biogenetic pathways of 1 and 2 are proposed to involve Diels-Alder and nucleophilic addition reactions. Both 1 and 2 induced significant G2/M-phase cell-cycle arrest. Furthermore, we found that merocytochalasans induce apoptosis in leukemia cells through the activation of caspase-3 and the degradation of PARP.
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Hucheng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Chen
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650204, China.
authors.forename: Xiao-Nian
authors.initials: XN
authors.lastname: Li
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650204, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Zengwei
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Guangmin
authors.initials: G
authors.lastname: Yao
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. zhangyh@mails.tjmu.edu.cn.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D001230:Aspergillus / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003572:Cytochalasins / Q000737:chemistry / Q000494:pharmacology*; D019281:Dimerization; D009682:Magnetic Resonance Spectroscopy; D014961:X-Ray Diffraction
chemical_list: D003572:Cytochalasins
keywords: alkaloids; biological activity; fungal natural products; polycycles; structural elucidation