Four new antitumor metabolites isolated from a mutant 3-f-31 strain derived from Penicillium purpurogenum G59

Penicimutanolones A (1) and B (2), penicimutanolone A methyl ether (3), and penicimumide (4), four new antitumor metabolites, were isolated from a neomycin-resistant mutant of the marine-derived fungus Penicillium purpurogenum G59. The structures of the compounds were elucidated by spectroscopic met...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2018-10, Vol.158, p.548-558
Main Authors: Wang, Nan, Li, Chang-Wei, Cui, Cheng-Bin, Cai, Bing, Xu, Lan-Lan, Zhu, Hua-Jie
Format: Article
Language:English
Subjects:
Activation of silent biosynthetic pathway
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - isolation & purification
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Biological Products - chemistry
Biological Products - isolation & purification
Biological Products - pharmacology
Cell Line, Tumor
HCT116 Cells
Humans
Mice
Models, Molecular
Mutation
Neomycin resistance
Neoplasms - drug therapy
Penicillium - chemistry
Penicillium - genetics
Penicillium purpurogenum
Penicimumide
Penicimutanolones
Polyketides
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Summary:Penicimutanolones A (1) and B (2), penicimutanolone A methyl ether (3), and penicimumide (4), four new antitumor metabolites, were isolated from a neomycin-resistant mutant of the marine-derived fungus Penicillium purpurogenum G59. The structures of the compounds were elucidated by spectroscopic methods, and the absolute configurations were determined by X-ray crystallography and calculated ECD. In MTT and SRB assays, compounds 1–3 showed strong inhibitory effects on 14 human cancer cell lines. Compounds 1 and 2 maybe induce apoptosis of cancer cells mainly due to the inhibition of the expression of survivin, a client protein of HSP90. In addition, in vivo antitumor activity was observed for compound 1 in murine sarcoma HCT116 tumor-bearing Kunming mice, using docetaxel as a positive control. [Display omitted] •Four new antitumor metabolites were isolated from Penicillium purpurogenum G59.•The absolute structures were determined by X-ray and calculated ECD.•Compounds 1–3 showed strong inhibitory effects on 14 human cancer cell lines.•Compounds 1 and 2 could inhibit the expression of survivin.•Compound 1 showed medium anti-tumor activity in vivo.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2018.09.015