engleski

Novel reversed amidine benzothiazoles: design, synthesis, antitrypanosomal activity and ADME profiling

Trypanosomatid protozoan parasites have a significant socioeconomic impact worldwide [1]. Amongst them are parasites of the Trypanosoma brucei species, which cause sleeping sickness, also known as human African trypanosomiasis (HAT). The current drugs used to treat HAT, pentamidine, suramin, melarsoprol and nifurtimoxeflornithine combination therapy (NECT), are toxic and not always effective due to the appearance of drug- resistance [1]. Although the design of arylimidamides (AIAs) was inspired by diamidine antiprotozoal agent pentamidine, AIAs possess physicochemical properties that are distinct from those of diamidines. In the AIAs, the imino group is bound to an aniline nitrogen atom, lowering the pKa of the amidine and increasing the lipophilicity of the molecule compared to a dicationic diamidine compound [2]. Previous studies by our group [3, 4] have shown that nitrogen heterocycles, such as benzimidazole and benzothiazole derivatives with cationic amidine moiety, have good antiprotozoal potency. Herein, we have designed and synthesized the arylimidamide-benzothiazoles with diversification in the substituted phenoxy moieties, as central part, and right-hand side of a molecule to modulate physicochemical and biological properties. Besides antitrypanosomal activity, physicochemical and ADME properties of prepared analogues will so be presented.

arylimidamide ; benzothiazole ; antitrypanosomal activity ; ADME properties

nije evidentirano