title: Asperflavipine A: A Cytochalasan Heterotetramer Uniquely Defined by a Highly Complex Tetradecacyclic Ring System from Aspergillus flavipes QCS12.
abstract: Asperflavipines A (1) and B (2), two structurally complex merocytochalasans, were isolated from Aspergillus flavipes. Asperflavipine A (1), which contains two cytochalasan moieties and two epicoccine moieties, is the first cytochalasan heterotetramer to be discovered. It is uniquely defined by 5/6/11/5/6/5/6/5/6/5/5/11/6/5 fused tetradecacyclic rings with three continuous bridged ring systems. Asperflavipine B (2) is a cytochalasan heterotrimer containing a cytochalasan and two epicoccine moieties with a 5/6/11/5/5/6/5/6/5 nonacyclic ring system. The hypothetical biosynthesis of 1 and 2 is proposed to involve Diels-Alder and [3+2] cycloaddition reactions as key steps and reveals unparalleled plasticity in the biosynthesis of merocytochalasans. The existence of 1 adds a new dimension to the diversity of the cytochalasan family. Compound 1 showed moderate cytotoxicity and induced apoptosis in Jurkat, NB4, and HL60 cells through the activation of caspase-3 and degradation of poly(ADP-ribose) polymerase (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.identifier: 0000-0002-6672-0014
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.identifier: 0000-0003-2087-7769
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.identifier: 0000-0001-7713-7230
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: 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: Guangzheng
authors.initials: G
authors.lastname: Wei
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: 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: 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: Yonghui
authors.identifier: 0000-0002-7222-2142
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001230:Aspergillus / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D061565:Cycloaddition Reaction; D003572:Cytochalasins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D015394:Molecular Structure; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D003572:Cytochalasins; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3
keywords: biological activity; heterotetramers; heterotrimers; natural products; structure elucidation