Synthesis of new 4,4’-(1H-1,2,3-triazole)-bis(1H-pyrazol-5-ols) and prospects for their study as potential antitumor agent

Abstract

Abstract The aim of our work is to develop an efficient synthesis of a series of novel 4,4'-(1H-1,2,3-triazol)bis(1H-pyrazol-5-ols), synthesize the target substances, and perform molecular docking focusing on the interaction of the synthesized compounds with the active sites of known cytostatics targeting various stages of oncogenesis. Materials and methods. The structure and purity of the obtained substances were confirmed by 1H NMR spectroscopy, 13C NMR spectroscopy and LC/MS. Docking studies were performed for the substances synthesized using Autodock 4.2 software. Results and discussion. A series of novel 4,4'-(1H-1,2,3-triazol)bis(1H-pyrazol-5-ols) were synthesized via a tandem Knoevenagel–Michael reaction from two equivalents of 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one with various 1,2,3-triazole aldehydes catalyzed by ammonium acetate in ethanol in high yields. As a result of the analysis of the array of docking computations and a detailed analysis of the geometric arrangement in the active sites of tumour targets (C-abl kinase, deoxycytidine kinase (dCK), CSF1 receptor, EGFRK receptor, FOLR2 receptor, it was found that the synthesized derivatives may have antitumor effects through the mechanism of inhibition of the EGFRK receptor. Conclusions. According to the molecular docking data, the newly synthesized derivatives 4,4'-((1H-1,2,3-triazol-4-yl)methylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) may have an antitumor effect through the mechanism of EGFRK receptor inhibition