Atividade antimicrobiana e toxicidade do protótipo n-antipirino-3,4-dicloromaleimida e seus derivados

Abstract

Cyclic imides have presented interesting biological properties, such as analgesic, antispasmodic, antitumoral, anti-inflammatory and in particular, antimicrobial effects. It can be obtained from natural sources, or through organic synthesis. In the present study, eighteen molecules of cyclic imides belonging to the subclass maleimides were synthesized from the prototype N-antipirino-3,4-dicloromaleimide, in order to evaluate the antimicrobial activity and toxicity potential of these substances. The antibacterial and antifungal activity was determined by the agar dilution method. To evaluate the toxicity, brine shrimp Artemia salina was used, and the yeast Saccharomyces cerevisiae. Finally, the mutagenic potential was determined, using the Ames test. Amongst the nineteen maleimides tested, six presented activity against yeast and/or dermatophytes and/or opportunist fungi, and the substance Nantipirine 3-chlorine-4-[benzylamine maleimide] (19) was the only one that showed activity to the three types of fungi. No antibacterial activity was observed for the substances at the maximum tested concentration (100 μg/mL). Regarding the potential toxicity, of the nineteen substances, it was verified that three of them fitted the criteria used for moderated toxicity in Artemia salina (LC50 since 86,23 to 94,15 μg/mL). However none of these substances presented antimicrobial activity. The other maleimides was considered atoxic (LC50 > 250 μg/mL). In the cell toxicity using strains of Saccharomyces cerevisiae, it was observed that only maleimide 07 showed toxic potential at the maximum concentration used (1000 μg/mL). None of nineteen maleimides studied showed mutagenic capacity in the Ames test at the maximum tested concentration (5 mg/mL). Thus, maleimides proved to be an interesting source of antifungal agents with low toxic potential