The invention relates to prepn. of aloe-emodin (AE) derivs. such as I [R = satd. or unsatd. linear or branched aliph. polycarboxylic acid, arylic polycarboxylic acid, amino acid, acetal of an amino sugar, inorg. acid], for their use as anticancer drugs. Thus, reaction between aloe-emodin with Boc-L-Ala-OSu provided II (R = Boc), which upon deprotection and treatment with concd. trifluoroacetic acid, afforded II [R = H.CF3CO2H (III)]. I show a specific cytotoxicity to tumor cells, also of neuroectodermal origin, to which they may in particular act as aloe-emodin prodrugs. Pharmaceutical compns. contg. I may be used in the treatment of neoplasias. It has surprisingly been found that aloe-emodin derivs. in position 3' (bearing either a pos. or neg. charge) exhibit improved soly. properties and, at the same time, in vitro show cytotoxicity to tumor cells, also of neuroectodermal origin. III exhibited cytotoxicity [EC50 = 6.7 μM, EC50 = 6.7 μM, and EC50 = 5 μM against neurolastoma (S-J-R-KP), neurolastoma (IMR-5), and adenocarcinoma (LoVo 109), resp].

Preparation of aloe-emodin derivatives and their use in the treatment of neoplasias

PALU', GIORGIO;CARLI, MODESTO OTTAVIANO;PECERE, TERESA;ZAGOTTO, GIUSEPPE
2002

Abstract

The invention relates to prepn. of aloe-emodin (AE) derivs. such as I [R = satd. or unsatd. linear or branched aliph. polycarboxylic acid, arylic polycarboxylic acid, amino acid, acetal of an amino sugar, inorg. acid], for their use as anticancer drugs. Thus, reaction between aloe-emodin with Boc-L-Ala-OSu provided II (R = Boc), which upon deprotection and treatment with concd. trifluoroacetic acid, afforded II [R = H.CF3CO2H (III)]. I show a specific cytotoxicity to tumor cells, also of neuroectodermal origin, to which they may in particular act as aloe-emodin prodrugs. Pharmaceutical compns. contg. I may be used in the treatment of neoplasias. It has surprisingly been found that aloe-emodin derivs. in position 3' (bearing either a pos. or neg. charge) exhibit improved soly. properties and, at the same time, in vitro show cytotoxicity to tumor cells, also of neuroectodermal origin. III exhibited cytotoxicity [EC50 = 6.7 μM, EC50 = 6.7 μM, and EC50 = 5 μM against neurolastoma (S-J-R-KP), neurolastoma (IMR-5), and adenocarcinoma (LoVo 109), resp].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/1465573
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