Affiliation:
1. Department of Pesticide Chemistry and Technology, Faculty of Agriculture, 21545-El-Shatby, Alexandria University, Alexandria, Egypt
Abstract
Background:
1,2,4-Triazoles are important five-membered heterocyclic scaffolds due to their
extensive biological activities. These products have been an area of growing interest to many
researchers around the world as of their diverse biological activities including antifungal and
antibacterial activity against broad spectrum of microbial pathogens.
Methods:
A series of 2-((1H-1,2,4-triazol-1-yl)methyl) derivatives was designed, synthesized and evaluated
as antifungal agents against five plant pathogenic fungi (Alternaria tennis, Botryodiplodia
theobromae, Fusarium moniliforme, Fusarium oxysporum and Helminthosporium turcicum) to meet the
urgent need of new antifungal agents with improved activity and broader spectrum. In silico studies
including pharmacophore modeling, virtual screening, drug-likeness analysis and ADMET prediction
were examined. In addition, the elucidation of the activity is based on the molecular docking to the active
site of the Sterol 14α-Demethylase Cytochrome P450 (CYP51) was investigated.
Results:
The results of antifungal activity indicated that the compounds containing tert or sec-butyl as
hydrophobic substituents on a phenyl ring significantly increased the activity (compounds 4, 5 and 6)
with EC50 in the range of 8-84 mg/L of all tested fungi. The pharmacophore modeling produced an
accurate projecting model (Hypo 1) from these derivatives. The superlative Hypo1 consists of three
features counting two hydrogen bond acceptors (HBA) and one hydrophobic (HYD). The docking
results showed approximately a similar binding degree at the active sites of the fungal enzyme (CYP51)
as a standard fungicide penconazole.
Conclusion:
According to data obtained, some derivatives, especially those with tert or sec-butyl substituents
on the phenyl ring, were more potent against phytopathogenic fungi. These compounds (e.g., 4,
5, and 6) should develop into new potential fungicides as a desirable activity.
Publisher
Bentham Science Publishers Ltd.
Subject
General Pharmacology, Toxicology and Pharmaceutics