| Abstrakt: |
Objective: A series of 4-amino-5-((2,4-substituted phenoxy)methyl)-4H-1,2,4-triazole-3-thiol derivatives (Ia–Ib) were synthesized and tested as aromatase enzyme inhibitor. Methods: 4-Amino-5-((2,4-substituted phenoxy)methyl)-4H-1,2,4-triazole-3-thiol derivatives (Ia–Ib) were synthesized via fusion of substituted phenoxycarboxylic acid derivatives with thiocarbohydrazide. Three series of the newly title compounds were prepared by reaction of (Ia–Ib) with aromatic acid derivatives in presence of POCl3 to give [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives (IIa–IIh) or by reaction with phenacyl bromide derivatives in presence of sodium acetate to produce [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives (IIIa–IIIh). Moreover, (Ia–Ib) were used as a precursor for synthesizing of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives (Va–Vd) by reaction with dibromochalcone compounds (IVa–IVb) in presence of triethylamine. The aromatase activities of the newly created compounds were examined. Results and Discussion: Seven triazoles were shown to have significant aromatase inhibitory activity (IC50 = 0.07–1.92 µM). It's interesting to note that analogue (Vb), which substituted a p-chlorophenyl ring at the triazole ring, had the greatest aromatase-inhibitory action (IC50 = 70 µM). Conclusions: The result of the present work indicated that compound (Vb) would be valuable as a potent anticancer agent. Moreover, docking study has been done into aromatase cytochrome P450 enzyme active site (PDB ID: 3EQM) for lead optimization of the aforementioned compounds as prospective tyrosine kinase inhibitors. [ABSTRACT FROM AUTHOR] |
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