engleski

Synthesis, anti-proliferative activity and 3D- QSAR analysis of novel series of amidino- substituted aryl-bisbenzazoles

Amidino-substituted benzazole compounds show a wide spectrum of biological activity and are investigated by several research groups during last 40 years. Our recent results revealed strong anti-proliferative effects on some tumour cell lines for isomeric imidazolinyl- substituted phenylene-bisbenzothiazole and imidazolinyl- substituted phenyl- and naphtylbenzothiazoles. These findings have led us to further investigate this class of compounds by introducing different types of amidinic substituents and heteroaromatic substructure, namely benzothiazole, benzimidazole and benzoxazole. Presented compounds were synthesized by condensation reaction of amidino- substituted 2 aminothiophenols, 2-aminophenols, bis(2- aminophenyl) disulphides or o- phenylenediamines with isomeric benzene and naphthalene dialdehydes or dicarboxylic acids. Anti proliferative activity screening for these novel series of dicationic compounds was performed in vitro on four tumour cell lines (SW620, HepG2, CFPAC-1 and HeLa) as well as on normal human fibroblasts (HFF). In order to identify molecular properties that are correlated with anti- proliferative activity, 3D-QSAR models for tested tumour cell lines were derived based on obtained anti- proliferative activities. All tested compounds showed strong to moderate anti- proliferative activity depending on the type of amidinic substituent as well as heteroatom in benzazole moiety.

amidine, bisbenzazole, anti-proliferative activity, QSAR

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