Alkaloids from a deep ocean sediment-derived fungus Penicillium sp. and their antitumor activities.
Four new alkaloids, including two new meleagrin analogs, meleagrin D (1) and E (2), and two new diketopiperazines, roquefortine H (3) and I (4), were isolated from a deep ocean sediment-derived fungus Penicillium sp. Meleagrin D (1) and E (2) possess unprecedented acetate-mevalonate-derived side chains on the imidazole moiety. These new meleagrins showed weak cytotoxicity against the A-549 cell line, whereas meleagrin B (5) and meleagrin (6), which were isolated previously from the same strain, induced HL-60 cell apoptosis or arrested the cell cycle through G(2)/M phase, respectively. The results indicate that the distinct substitutions on the imidazole ring significantly influence the cytotoxicity of the meleagrin alkaloids.
Du
Lin
L
Key Laboratory of Marine Drugs, Chinese Ministry of Education School of Medicine and Pharmacy, Institute of Marine Drugs and Food, Ocean University of China, Qingdao, PR China.
Feng
Teng
T
Zhao
Boyu
B
Li
Dehai
D
Cai
Shengxin
S
Zhu
Tianjiao
T
Wang
Fengping
F
Xiao
Xiang
X
Gu
Qianqun
Q
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D019015:Geologic Sediments; D018922:HL-60 Cells; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D010407:Penicillium / Q000737:chemistry*; D012988:Soil Microbiology; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D000470:Alkaloids; D000970:Antineoplastic Agents; D004224:Diterpenes; D007093:Imidazoles