ombretastatin derivs., such as I [R1, R2, R3, R4 = H, OH, OMe, OCH2O, NO2, F, Cl, Br, OPO3H2, OCH2OPO3H2 and their disodium salts; R1R2 = CR8:CR9X; R8, R9 = H, OH, NO2, NH2, halo, OPO3H2, OCH2OPO3H2 and their disodium salts; X = O, S, N; Y = CR5:CR6-cis or trans; II, III; R5, R6 = H, halo; R7 = H, OMe, SO2Ph; Ar = aryl, heterocyclyl], are prepd. and evaluated for their cytotoxic activity. The prepd. compds., though chem. related to the structure of cis/trans-combretastatin, do not always bind tubulin, but nevertheless exhibit cytotoxic activity of interest in the oncol. field as anticancer and/or antiangiogenic agents. Thus, combretastatin deriv. IV was prepd. via a multistep synthetic sequence starting from 2-thienylcarboxaldehyde, diethylsuccinate and (3,4,5-trimethoxybenzyl)triphenylphosphonium bromide. IV exhibited cytotoxicity against bovine microcirculatory endothelial cells (IC50 = 87±1 mM).
Preparation of combretastatin derivatives with cytotoxic activity
SIMONI, Daniele;ROMAGNOLI, Romeo;
2005
Abstract
ombretastatin derivs., such as I [R1, R2, R3, R4 = H, OH, OMe, OCH2O, NO2, F, Cl, Br, OPO3H2, OCH2OPO3H2 and their disodium salts; R1R2 = CR8:CR9X; R8, R9 = H, OH, NO2, NH2, halo, OPO3H2, OCH2OPO3H2 and their disodium salts; X = O, S, N; Y = CR5:CR6-cis or trans; II, III; R5, R6 = H, halo; R7 = H, OMe, SO2Ph; Ar = aryl, heterocyclyl], are prepd. and evaluated for their cytotoxic activity. The prepd. compds., though chem. related to the structure of cis/trans-combretastatin, do not always bind tubulin, but nevertheless exhibit cytotoxic activity of interest in the oncol. field as anticancer and/or antiangiogenic agents. Thus, combretastatin deriv. IV was prepd. via a multistep synthetic sequence starting from 2-thienylcarboxaldehyde, diethylsuccinate and (3,4,5-trimethoxybenzyl)triphenylphosphonium bromide. IV exhibited cytotoxicity against bovine microcirculatory endothelial cells (IC50 = 87±1 mM).I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
