Polyoxygenated cinnamoylcoumarins as conformationally constrained analogs of cytotoxic diarylpentanoids: Synthesis and biological activity

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• 作者：Fatemeh Molaverdi ; Mehdi Khoobi ; Saeed Emami ; Masoumeh Alipour ; Omidreza Firuzi ; Alireza Foroumadi ; Gholamreza Dehghan ; Ramin Miri ; Fatemeh Shaki ; Farnaz Jafarpour ; Abbas Shafiee
• 关键词：Curcuminoids ; Diarylpentanoids ; Coumarin ; Anti-cancer ; Cytotoxic agent ; Antioxidant activity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：October, 2013
• 年：2013
• 卷：68
• 期：Complete
• 页码：103-110
• 全文大小：544 K

文摘

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?¡Ü?5.5?¦ÌM). 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.