Synthesis of symmetrical 1,4-disubstituted 1,2,3-bistriazoles obtained by optimized CuAAC conditions and evaluation of antifungal and antitrypanosomastid activities

The bi- and bistriazoles1 gained significant attention for their potential application in pharmaceutical,2 supramolecular,3 biological4 and organometallic5 chemistry. Due this, some symmetrical 1,4-disubstituted 1,2,3-triazoles were synthesized from bisazides and terminal alkynes by CuAAC optimized methodology. Alkyl and phenyl 4-substituted bistriazoles were obtained in good to excellent yields while oxygenated derivatives failed or led to desired products in low yields. These derivatives had their cytotoxic activities evaluated against fungal and leishmanial cells. The best result to antifungal activity was reached by bistriazole 11a, that showed the same MIC of fluconazole (32 μg mL-1) against Candida krusei ATCC 6258, an emerging and potentially multidrug-resistant fungal pathogen. Due their intrinsically biological activity versatility, five derivatives compounds showed inhibition of leishmanicidal activity between 15.0 and 20.0% at concentrations of 20 and 40.0 μg mL-1. Among them, the derivative 13a showed best IC50 value of 63.34 μg mL-1 (182.86 μM).