Antifungal activity of guanidine compounds

Abstract

Guanidinic compounds are a class of compounds distributed in nature but also synthesized in vitro with a wide variety of applicability. One of the potentials of those molecules is antimicrobial activity. In that sense, although mainly limited to immunocompromised people, fungi pathogens are a cause of concern, even more so after the COVID-19 pandemic. Susceptible groups and increased geographical distribution, besides drug toxicity, resistance, and high costs, made the World Health Organization (WHO) establish a guideline for research and public health politics against different fungi opportunist agents. Our present work evaluated the antifungal activity of 11 guanidine compounds (one of them synthesized for the first time) against six fungi species in the WHO Fungi Priority Pathogens List and their potential for antimicrobial selectivity. The newly synthesized compound, named LQOF-G2-S, was successfully obtained and chemically characterized as spermidine tri-substituted by guanidine moieties in benzylamine-4-bromoaniline groups, and it presented the best antifungal activity and selectivity among the others. It was the only compound active against Candida spp.; however, its activity was more promising against Cryptococcus neoformans, Cryptococcus gattii, and even more against Paracoccidioides brasiliensis and Paracoccidioides lutzii, with a selective index higher than 10. The LQOF-G2-S potential opened up the opportunity to design and evaluate other similar compounds, contributing to finding new effective, less toxic, and more affordable compounds for fungi treatment.

Keywords: Candida; Cytotoxicity; Spermidine; WHO fungi priority pathogens list.