ABSTRACT
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.
Subject(s)
Annonaceae/chemistry , Antibiotics, Antineoplastic/pharmacology , Lactones/pharmacology , Styrenes/pharmacology , Animals , Antibiotics, Antineoplastic/chemical synthesis , Antibiotics, Antineoplastic/chemistry , Drug Screening Assays, Antitumor , Humans , Lactones/chemical synthesis , Lactones/chemistry , Styrenes/chemical synthesis , Styrenes/chemistry , Tumor Cells, CulturedABSTRACT
Synthesis and antitumor activity of goniofufurone analogues 15, 16, 17, 33, and 46 is reported. Key step in the synthesis is Pd (II) mediated oxidative cyclisation of vinyl-(hydroxy) furans 18, 19 to the corresponding lactols 32, 43. Cytotoxicities of 15, 16, 17, 33, and 46 tested against six human cancer cell lines are reported. Change of stereochemistry at C-5, C-6 and C-7 position of goniofufurone (1) did not enhance the cytotoxicities significantly.
