title: Diarylheptanoids from the bark of black alder inhibit the growth of sensitive and multi-drug resistant non-small cell lung carcinoma cells.
abstract: An extended study of minor diarylheptanoids from the bark of black alder has resulted in the isolation of twenty diarylheptanoids, ten of which have not previously been reported (14-18, 20-24). The structures and configurations of all compounds were elucidated by NMR, HRESIMS, UV, IR, and CD. The anti-cancer potency of twenty diarylheptanoids and four previously isolated compounds (7, 10, 12, 13) was investigated in human non-small cell lung carcinoma cell lines (sensitive and multi-drug resistant variants) as well as in normal human keratinocytes. Diarylheptanoids with a p-coumaroyl group, 14 and 18, platyphylloside (1), platyphyllonol-5-O-β-D-xylopyranoside (2), alnuside B (4) and hirsutenone (9) exhibited strong anti-cancer activity, considerably higher than diarylheptanoid curcumin, which served as a positive control. Compounds 4, 9, 14, and 18 displayed significant selectivity towards the cancer cells. Structure/activity analysis of twenty-four closely related diarylheptanoids revealed a high dependence of cytotoxic action on the presence of a carbonyl group at C-3. Substitution of a heptane chain on C-5 and a number of hydroxyl groups in the aromatic rings also emerged as a significant structural feature that influenced their cytotoxic potential.
authors.affiliation: Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 12-16, 11058 Belgrade, Serbia. Electronic address: mironov76@yahoo.com.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Novaković
authors.affiliation: Institute for Biological Research, Department of Neurobiology, University of Belgrade, Despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Pešić
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11058 Belgrade, Serbia.
authors.forename: Snežana
authors.initials: S
authors.lastname: Trifunović
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11058 Belgrade, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Vučković
authors.affiliation: Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 12-16, 11058 Belgrade, Serbia.
authors.forename: Nina
authors.initials: N
authors.lastname: Todorović
authors.affiliation: Institute for Biological Research, Department of Neurobiology, University of Belgrade, Despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Podolski-Renić
authors.affiliation: Institute for Biological Research, Department of Neurobiology, University of Belgrade, Despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Dinić
authors.affiliation: Institute for Biological Research, Department of Neurobiology, University of Belgrade, Despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Stojković
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11058 Belgrade, Serbia.
authors.forename: Vele
authors.initials: V
authors.lastname: Tešević
authors.affiliation: Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 12-16, 11058 Belgrade, Serbia.
authors.forename: Vlatka
authors.initials: V
authors.lastname: Vajs
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11058 Belgrade, Serbia.
authors.forename: Slobodan
authors.initials: S
authors.lastname: Milosavljević
mesh_terms: D029661:Alnus / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D036381:Diarylheptanoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006027:Glycosides; D006536:Heptanes / Q000494:pharmacology; D030017:Ilex / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D024301:Plant Bark / Q000737:chemistry; D055752:Small Cell Lung Carcinoma
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002396:Catechols; D036381:Diarylheptanoids; D006027:Glycosides; D006536:Heptanes; C000588876:alnuside B; C508777:hirsutenone; C000588875:platyphyllonol-5-O-beta-D-xylopyranoside; C000588874:platyphylloside
keywords: Anti-cancer activity; Black alder; Diarylheptanoids; HPLC-DAD; Multi-drug resistance; NMR analysis