title: Polyoxygenated cinnamoylcoumarins as conformationally constrained analogs of cytotoxic diarylpentanoids: synthesis and biological activity.
abstract: A series of polyoxygenated cinnamoylcoumarins was synthesized as conformationally constrained analogs of cytotoxic diarylpentanoids. The title compounds were tested against the viability of human chronic myelogenous leukemia (K562), human acute lymphoblastic leukemia (MOLT-4) and human breast adenocarcinoma (MCF-7) cell lines by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Among them, all 6- or 7-hydroxylated compounds 6a-h exhibited remarkable cytotoxic activity. Particularly, 7-hydroxycoumarin analog 6h showed good antiproliferative activity against all tested cell lines (IC50 values≤5.5 μM). The preliminary study with selected compounds 6e and 6f showed that reactivity towards mitochondrial thiol compounds cab be considered as cytotoxic mechanism of designed compounds. Furthermore, the antioxidant activity evaluation of synthesized compounds showed that hydroxylated compounds had antioxidative potential at higher concentrations.
authors: School of Chemistry, College of Science, University of Tehran, Tehran, Iran.
authors: Fatemeh
authors: F
authors: Molaverdi
authors: Mehdi
authors: M
authors: Khoobi
authors: Saeed
authors: S
authors: Emami
authors: Masoumeh
authors: M
authors: Alipour
authors: Omidreza
authors: O
authors: Firuzi
authors: Alireza
authors: A
authors: Foroumadi
authors: Gholamreza
authors: G
authors: Dehghan
authors: Ramin
authors: R
authors: Miri
authors: Fatemeh
authors: F
authors: Shaki
authors: Farnaz
authors: F
authors: Jafarpour
authors: Abbas
authors: A
authors: Shafiee
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry; D000439:Pentanols / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D003374:Coumarins; D000439:Pentanols; D010100:Oxygen
keywords: Anti-cancer; Antioxidant activity; Coumarin; Curcuminoids; Cytotoxic agent; Diarylpentanoids