Synthesis and Evaluating the Anticandidal Activities of Triazino[4,3-a]Quinolinecarboxylate Derivatives: A Promising...

This study aimed to synthesize novel triazino[4,3-a]quinolinecarboxylate compounds (4, 6, 8, and 10) and evaluate these compounds for their antifungal activity against Candida species. Compound 8 was a standout candidate which demonstrated superior efficacy against C. albicans (minimum inhibitory concentration [MIC] = 45 µg/mL), C. glabrata (MIC = 32 µg/mL), C. parapsilosis (MIC = 36 µg/mL) and C. guilliermondii (MIC = 32 µg/mL) compared to Miconazole (MIC = 50-60 µg/mL). Furthermore, the induced morphological and ultra-structural changes by compound 8 on Candida cells are analyzed by light and transmission electron microscopy. Significant alterations in the viability and the architecture of Candida cells highlight the potential of compound 8 as a lead for further use as an antifungal drug. SARs displayed that substitution with the cyano group (as in compounds 8 and 10) was critical for anticandida potency. A molecular docking study of the most active compounds 8 and 10 was conducted inside 14α-demethylase (CYP51) to predict the binding mode of these compounds as antifungal. The most active compound 8 (MIC = 32-45 µg/mL) demonstrated the highest binding energy score which is equal to -8.93 kcal/mol. The findings of the in vitro anticandidal potential have been supported by molecular docking studies.