Design, synthesis and in vitro biological studies of novel triazoles with potent and broad-spectrum antifungal activity

Abstract

A series of novel triazole derivatives containing aryl-propanamide side chains was designed and synthesised. In vitro antifungal activity studies demonstrated that most of the compounds inhibited the growth of six human pathogenic fungi. In particular, parts of phenyl-propionamide-containing compounds had excellent, broad-spectrum antifungal activity against Candida albicans SC5314, Cryptococcus neoformans 22-21, Candida glabrata 537 and Candida parapsilosis 22-20 with MIC values in the range of ≤0.125 µg/mL–4.0 µg/mL. In addition, compounds A1 , A2 , A6 , A12 and A15 showed inhibitory activities against fluconazole-resistant Candida albicans and Candida auris . Preliminary structure-activity relationships (SARs) are also summarised. Moreover, GC-MS analysis demonstrated that A1 , A3 , and A9 interfered with the C. albicans ergosterol biosynthesis pathway by inhibiting Cyp51. Molecular docking studies elucidated the binding modes of A3 and A9 with Cyp51. These compounds with low haemolytic activity and favourable ADME/T properties are promising for the development of novel antifungal agents.

Inhibition of apoptosis and biofilm formation in Candida auris by click-synthesized triazole-bridged quinoline derivatives

“…The broad-spectrum activity against various fungal strains of triazole analogues has been demonstrated by various researchers. 28–30…”

“…The broad-spectrum activity against various fungal strains of triazole analogues has been demonstrated by various researchers. [28][29][30] 2.2.2 Anti-biolm activity. The impact of the QT7 over 24 h mature biolm was determined with the help of crystal violet assay and Fig.…”

“…The hemolytic activity of the novel QT7 was evaluated using horse-red blood cells (h-RBC). 29,45 Briey, 10 mL h-RBCs were centrifuged (2000 rpm, 10 minutes), and the pellet was washed thrice with chilled PBS and resuspended in the same to make a 10% h-RBC solution (stock solution). The stock solution was diluted ten times and a 1000 mL aliquot was treated with various concentrations of QT7 (1/2× MIC, MIC and MFC), PBS (negative control) and 10% Triton X-100 (positive control).…”

Discovery of Novel α,β-Unsaturated Amide Derivatives as Candidate Antifungals to Overcome Fungal Resistance

“…We employed the previously mentioned techniques to carry out the GC-MS analysis. 34 TEM Experiment. The test strain used was C. albicans SC5314, and the positive control chosen was fluconazole.…”