Abstract :

Fungal infection is a significant global health challenge in part due to the emergence of strains exhibiting resistance to nearlyall classes of antifungals. This underscores the urgent need for the development of new antifungal agents that can circumventthis burgeoning problem. For the present research, a new selected set of pyrazolo[5,1-c][1,2,4]triazine derivatives 3a–g wasprepared in high yield via the reaction of N1-(5-methylpyrazol-3-yl)hydrazonoyl chloride 1 with morpholine, thiomorpholine,4-phenylpiperidine and N-(substituted)piperazines. The new compounds were evaluated for their in vitro antifungal andantibacterial activities. The screening revealed compounds with specific activity against pathogenic fungi, including Candidaalbicans, Candida auris, and Cryptococcus. Compound 3d, which incorporated N-phenylpiperazine moiety, exhibited thehighest growth inhibition against C. albicans with a minimum inhibitory concentration of 16 μg/mL. The compounds weresuperior to fluconazole in inhibiting Candida biofilm mass at sub-inhibitory concentration. Furthermore, the MTS assayconfirmed that compounds 1 and 3d exhibited an excellent toxicity profile (not toxic, up to 256 μg/mL, for mammaliancells). Collectively, the presented results demonstrate that the synthesized pyrazolo-triazines warrant further explorationfor potential use as antifungal agents.