Synthesis of vanillin-coupled 1, 2, 3-triazoles via click reaction: molecular modeling, structure activity correlation by DFT, ADMET and antibacterial studies

Abstract

The newly vanillin-functionalized 1, 2, 3-triazoles (4b–e) were synthesized by 1, 3-dipolar cycloaddition reaction through click chemistry approach. The characterization of significant compounds (4b–e) was carried out through EI-MS, ¹H NMR, and IR spectroscopic techniques. These compounds (4b–e) showed a characteristic peak of aldehyde proton (CHO) as a singlet at 9.8 ppm with another prominent peak of triazole ring proton (C = CHN) in 8.20–8.25 ppm region. The IR frequency signals of (C = C) appeared at 2100–2200 cm⁻¹ and (C = O) of aldehyde carbonyl at 1700–1705 cm⁻¹. The antibacterial investigations with biofilm inhibition method were carried against four strains Mammaliicoccus sciuri (KSA01), M. sciuri (KSA02), Staphylococcus aureus (KSA03), and S. aureus (KSA04). The compounds (4d) and (4e) were more active than standard with 0.006 µg/ml MIC and MBC values for (KSA02) and (KSA03). The structure activity relationship analysis through molecular docking further supported the antimicrobial revelations for the same scaffolds having high inhibition potential that was further explored by electronic structure studies and HOMO/LUMO mapping applying DFT method with B3LYP/6-311G(d, p) level of theory. ADMET profiling in addition, revealed the (4d and 4e) to have all blood–brain barrier permeability and human intestinal absorption.

Graphical abstract

Synthesized vanillin-functionalized 1, 2, 3-triazoles (4b–e) via click chemistry approach for antibacterial potential. Synthesized compounds were characterized through EI-MS, ¹H NMR, and IR spectroscopy. (4d) and (4e) outshone standards in biofilm inhibition against M. sciuri and S. aureus strains. Molecular docking and DFT studies supported their high inhibition potential. ADMET profile showing promising BBB permeability and intestinal absorption.