Synthesis, structural characterization, and prospects for new cobalt (II) complexes with thiocarbamoyl-pyrazoline ligands as promising antifungal agents

Abstract

Candida spp. cause invasive fungal infections. One species, Candida glabrata, may present intrinsic resistance to conventional antifungal agents, thereby increasing mortality rates in hospitalized patients. In this context, metal complexes present an alternative for the development of new antifungal drugs owing to their biological and pharmacological activities demonstrated in studies in the last decades. Accordingly, in this study we have synthesized and characterized two new Co(II) complexes with thiocarbamoyl-pyrazoline ligands to assess their antimicrobial, mutagenic, and cytotoxic potential. For antimicrobial activity, the broth microdilution method was performed against ATCC strains of Candida spp. and fluconazole dose-dependent isolates of C. glabrata obtained from urine samples. The Ames test was used to assess mutagenic potential. The reduction method of the MTS reagent (3 [4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium) was performed with HeLa, SiHa, and Vero cells to determine cytotoxicity. Both complexes exhibited fungistatic and fungicidal activity for the yeasts used in the study, demonstrating greater potential for C. glabrata ATCC 2001 and the C. glabrata CG66 isolate with a Minimum Inhibitory Concentration MIC from 3.90 to 7.81 μg mL−1 and fungicidal action from 7.81 to 15.62 μg mL−1. The complexes inhibited and degraded biofilms by up to 90% and did not present mutagenic and cytotoxic potential at the concentrations evaluated for MIC. Thus, the complexes examined herein suggest promising alternatives for the development of new antifungal drugs.