title: Plasticity in gilvocarcin-type C-glycoside pathways: discovery and antitumoral evaluation of polycarcin V from Streptomyces polyformus.
abstract: Gilvocarcin-type polyketide glycosides represent some of the most powerful antitumor therapeutics. Bioactivity-guided fractionation of a culture extract of Streptomyces polyformus sp. nov. (YIM 33176) yielded the known gilvocarcin V (2) and a novel related compound, polycarcin V (1). Structure elucidation by NMR and chemical derivatization revealed that the congener (1) features a C-glycosidically linked alpha-L-rhamnopyranosyl moiety in lieu of the D-fucofuranose. The concomitant production of two distinct furanosyl and pyranosyl C-glycosides that share the same aglycone is unprecedented in bacteria. A conversion of both isoforms via a quinone methide intermediate can be ruled out, thus pointing to two individual C-glycosylation pathways. Cytotoxicity profiling of polycarcin V in a panel of 37 tumor cell lines indicated significant antitumoral activity with a pronounced selectivity for non-small-cell lung cancer, breast cancer and melanoma cells. As the antiproliferative fingerprint is identical to that of actinomycin D, the known DNA interaction of gilvocarcins was established as a general principle of antitumorigenic activity.
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Beutenbergstr. 11a, D-07745, Jena, Germany.
authors.forename: Yi-qing
authors.initials: YQ
authors.lastname: Li
authors.forename: Xue-shi
authors.initials: XS
authors.lastname: Huang
authors.forename: Keishi
authors.initials: K
authors.lastname: Ishida
authors.forename: Armin
authors.initials: A
authors.lastname: Maier
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kelter
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.forename: Gundela
authors.initials: G
authors.lastname: Peschel
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Menzel
authors.forename: Ming-gang
authors.initials: MG
authors.lastname: Li
authors.forename: Meng-liang
authors.initials: ML
authors.lastname: Wen
authors.forename: Li-hua
authors.initials: LH
authors.lastname: Xu
authors.forename: Susanne
authors.initials: S
authors.lastname: Grabley
authors.forename: Heinz-Herbert
authors.initials: HH
authors.lastname: Fiebig
authors.forename: Cheng-lin
authors.initials: CL
authors.lastname: Jiang
authors.forename: Christian
authors.initials: C
authors.lastname: Hertweck
authors.forename: Isabel
authors.initials: I
authors.lastname: Sattler
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D006027:Glycosides / Q000032:analysis / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D013302:Streptomyces / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D006027:Glycosides; C534478:polycarcin V; C031781:gilvocarcin V