Exploring 1,2,3-triazole derivatives by using in vitro and in silico assays to target new antifungal agents and treat Candidiasis

• Published in: Medicinal chemistry research 2017-03, Vol.26 (3), p.680-689
• Main Authors: Santos, Taísa F., de Jesus, Jéssica B., Neufeld, Paulo M., Jordão, Alessandro K., Campos, Vinícius R., Cunha, Anna C., Castro, Helena C., de Souza, Maria C. B. V., Ferreira, Vitor F., Rodrigues, Carlos R., Abreu, Paula A.
• Format: Article
• Language: English
• Subjects: Antifungal activity; Antifungal agents; Atomic properties; Biochemistry; Biomedical and Life Sciences; Biomedicine; Candidiasis; Cell Biology; Chemical bonds; Drugs; Fungicides; Hydrogen bonds; Immunodeficiency; Medical importance; Minimum inhibitory concentration; Molecular orbitals; Original Research; Pharmacology/Toxicology; Public health; Side effects; Triazoles
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-017-1789-x

Candidiasis is a serious public health problem that currently affects not only immunodeficient patients with predisposing conditions, but also immunocompetent individuals. Thus, the search for new antifungal agents is required also due to the emergence of resistant strains and to the side effects of the available drugs. The aim of this study is to evaluate the in vitro antifungal profile of nine synthetic 1,2,3-triazole derivatives against four Candida species of medical importance ( C. albicans, C. tropicalis, C. parapsilosis , and C. krusei ), as well as to identify their in silico structure-activity relationship. Interestingly, the antifungal susceptibility tests showed the compound 5-methyl-1-(phenylamino)-1H-1,2,3-triazol-4-yl-methanol ( 2b ) with the lowest minimal inhibitory concentration value against C. albicans strain (MIC = 8 μg/mL) similar to other promissing compounds described in the literature. According to our in silico evaluation, some stereoelectronic properties (e.g., higher values of log S and lowest unoccupied molecular orbital energy and lower number of atoms, rotatable bonds and Hydrogen bond acceptors) were correlated with the antifungal activity detected. This series reinforced the potential of 1,2,3-triazole as a promising nucleus in the search for new antifungals and may help on designing new drugs for candidiasis.