title: Indole diketopiperazines from endophytic Chaetomium sp 88194 induce breast cancer cell apoptotic death.
abstract: Diketopiperazines are important secondary metabolites of the fungi with variety bioactivities. Several species belonging to genus Chaetomium produce compounds of this class, such as chetomin. To identify new antitumor agents, secondary metabolites of fungus Chaetomium sp 88194 were investigated and three new indole diketopiperazines, Chaetocochins G (1), Oidioperazines E (2) and Chetoseminudin E (3), along with two known compounds Chetoseminudins C (4) and N-acetyl-β-oxotryptamine (5), were obtained. Chaetocochins G and Chetoseminudin E were recrystallized in CHCl3 containing a small amount of MeOH, and their structures with absolute configuration were established by spectroscopic data interpretation and single-crystal X-ray diffraction analysis. The absolute configuration of Oidioperazines E was defined by comparing of experimental and calculated electronic circular dichroism spectra. These isolates were also evaluated the anticancer activity, and Chaetocochins G displayed more potent cytotoxicity in MCF-7 cells than the common chemotherapeutic agent (5-fluorouracil) associated with G2/M cell cycle arrest. More importantly, Chaetocochins G induced cell apoptotic death via caspase-3 induction and proteolytic cleavage of poly (ADP-ribose) polymerase, concomitantly with increased Bax and decreased Bcl-2 expression. Our findings suggested that indole diketopiperazines from endophytic Chaetomium sp 88194 may be potential resource for developing anti-cancer reagents.
authors: Department of Pharmacy, Wuhan First Hospital, Wuhan 430022, Hubei, People's Republic of China.
authors: Fu-qian
authors: FQ
authors: Wang
authors: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Qing-yi
authors: QY
authors: Tong
authors: Department of Pharmacy, Wuhan First Hospital, Wuhan 430022, Hubei, People's Republic of China.
authors: Hao-ran
authors: HR
authors: Ma
authors: Department of Pharmacy, Wuhan First Hospital, Wuhan 430022, Hubei, People's Republic of China.
authors: Hong-feng
authors: HF
authors: Xu
authors: Department of Pharmacy, Wuhan First Hospital, Wuhan 430022, Hubei, People's Republic of China.
authors: Song
authors: S
authors: Hu
authors: Department of Pharmacy, Wuhan First Hospital, Wuhan 430022, Hubei, People's Republic of China.
authors: Wei
authors: W
authors: Ma
authors: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Yong-bo
authors: YB
authors: Xue
authors: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Jun-jun
authors: JJ
authors: Liu
authors: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Jian-ping
authors: JP
authors: Wang
authors: Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Hong-ping
authors: HP
authors: Song
authors: Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Jin-wen
authors: JW
authors: Zhang
authors: Department of Pharmacy, Wuhan First Hospital, Wuhan 430022, Hubei, People's Republic of China.
authors: Geng
authors: G
authors: Zhang
authors: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Yong-hui
authors: YH
authors: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002597:Chaetomium / Q000378:metabolism*; D054659:Diketopiperazines / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D054659:Diketopiperazines; D007211:Indoles; C030374:indole