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3D Pharmacophore-based Ligand Alignment, Virtual Screening and Molecular Docking Protocols Towards the Discovery of 2-((1H-1,2,4-triazol-1- yl)methyl) Derivatives as Antifungal Inhibitors

[ Vol. 16 , Issue. 4 ]


Mohamed E. I. Badawy* and Saad R. El-Zemity   Pages 498 - 513 ( 16 )


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 broadspectrum of microbial pathogens

Methods: A series of 2-((1H-1,2,4-triazol-1-yl)methyl) derivativeswas designed, synthesized and eval-uated as antifungal agents against five plant pathogenic fungi (Alternaria tennis, Botryodiplodia theobromae, Fusarium moniliforme, Fusarium oxysporumandHelminthosporium turcicum) to meet the urgent need of new antifungal agents with improved activity and broader spectrum. In silicostudies including pharmacophore modeling,virtual screening, drug-likeness analysis andADMET prediction were examined. In addition, the elucidation of the activity is based on the molecular docking to the ac-tive site of the Sterol 14α-Demethylase Cytochrome P450 (CYP51) was investigated.

Results: The results of antifungal activity indicated that the compounds containing tertor sec-butyl as hydrophobic substituents on a phenyl ring significantly increased the activity (compounds 4, 5and 6) with EC50in 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 consistsof 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 tertor sec-butyl sub-stituents 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 desirableactivity.


2-((1H-1, 2, 4-triazol-1-yl)methyl) derivatives, Antifungal activity, 3D Pharmacophore modeling, Virtual screening, Docking, enzyme


Department of Pesticide Chemistry and Technology, Faculty of Agriculture, 21545-El-Shatby,Alexandria University, Alexandria, Department of Pesticide Chemistry and Technology, Faculty of Agriculture, 21545-El-Shatby,Alexandria University, Alexandria

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