engleski

New Class of Antitrypanosomal Agents Based on Amidino-Substituted Benzazoles: Design, Synthesis and Biological Evaluation

Human African Trypanosomiasis (HAT) is a life- threatening, neglected tropical disease, with around 60 million people at risk in 36 sub- Saharan African countries. The current drugs used to treat HAT, pentamidine, suramin, melarsoprol and nifurtimox-eflornithine combination therapy (NECT), are toxic and not always effective due to the appearance of drug-resistance. [1] In continuation of our scientific research based on the development of aromatic amidines as DNA- binding ligands and antitrypanosomal agents [2, 3], we have designed and synthesized novel amidino-substituted benzazole derivatives. Design of novel amidino derivatives was focused on diversification of three regions of target molecules: changing type of amidino substituent on left-hand side and type of aromatic and aliphatic substituents on right-hand side of a molecule, as well as changing central heterocycle from benzimidazole to benzothiazole to modulate biological properties. Novel amidino-substituted benzazole derivatives were synthesized through formation of benzimidazole moiety by oxidative coupling of o-phenylenediamines with aldehydes or by condensation of 2-aminothiophenoles with corresponding aldehydes. Compound with potent antitrypanosomal activity have been selected for investigation of their DNA/RNA binding affinities.

amidino derivatives, benzimidazole, benzothiazole, antitrypanosomal activity

nije evidentirano