Synthesis, Characterization, PASS Prediction and in silico ADME Studies of Ester and Ether Linked 1,4-Disubstituted 1,2,3-Triazoles Derivatives via Click Approach

Abstract

In the present investigation, we focused our interest on the synthesis of pharmacophoric units (quinoline and 1,2,3-triazole) linked through ester (3a-b) and (substituted aromatic ring and 1,2,3-triazole) linked through an ether (3c-h). The synthesis involves multiple sequence of reactions viz. diazotization reaction followed by nucleophilic substitution and finally Cu(I)-catalyzed alkyne azide cycloaddition reaction (CuAAC). The assigned structures of the compound were confirmed by 1H & 13C NMR and mass spectrometry. Prediction of activity spectra for substances (PASS) training set for the synthesized compounds were carried out using PASS software. Interestingly, PASS prediction of the compounds (3a-h) showed that the compounds are more potent as anti-inflammatory (Pa < 0.65) compared to antibacterial (Pa < 0.33) as well as antifungal agents (Pa < 0.35). Furthermore, these compounds were subjected to in silico ADMETox evaluation. All the compounds were found to pass the ADME evaluation and only few compounds passed the predicted toxicity evaluation. This work could be used as an initial approach in identifying potential novel molecules with promising activity and low toxicity.