Cytotoxic activity of styryl lactones and their derivatives.
Many studies that have been conducted to establish the cytotoxic potency of styryl lactones for several tumor cell lines is described. Extensive examination of the activity of more than 50 cytotoxic styryl lactones isolated/synthesized belonging to the genus goniothalamus representing future generation of antitumor drugs is described for the first time at the molecular level. Goniopypyrone (39) is the most cytotoxic compound followed by altholactone (+)-1 (10(-5) to 10(-7) molar for IC(50)). Enantiomer (-)-1 and three stereocongeners 2-4 did not exhibit any significant increase in cytotoxicity. Cytotoxicity of semisynthetically derived products 5-11 is discussed recognising 11-nitro altho-lactone (+)-5 as a promising lead compound. Eight membered styryl lactones 12a - 12e are substrates with important cytotoxicity explained by the inhibition of the mammalian mitochondrial respiratory chain complex I. Among C(7)-C(8) functionalised styryl lactones gonio diol (25) is the most active being selectively cytotoxic against A549 tumour cells. Goniofufurone (42) and several of its derivatives including one carbon homologues 43-50 were reported to be inactive.
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Organic Chemistry Division III, Fine Chemical Laboratory, Indian Institute of Chemical Technology, Hyderabad 500 007, India. haribabu@iict.ap.nic.in
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D000818:Animals; D029061:Annonaceae / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013343:Styrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D007783:Lactones; D013343:Styrenes