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

A series of novel triazole derivatives containing aryl-propanamide side chains was designed and synthesised. 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 SC5314, 22-21, 537 and 22-20 with MIC values in the range of ≤0.125 µg/mL-4.0 µg/mL. In addition, compounds , , , and showed inhibitory activities against fluconazole-resistant and . Preliminary structure-activity relationships (SARs) are also summarised. Moreover, GC-MS analysis demonstrated that , , and interfered with the ergosterol biosynthesis pathway by inhibiting Cyp51. Molecular docking studies elucidated the binding modes of and with Cyp51. These compounds with low haemolytic activity and favourable ADME/T properties are promising for the development of novel antifungal agents.