Pyrazoline Spiro-oxindole tethered 1,2,3-triazole hybrids: Design, synthesis, antimicrobial efficacy and molecular modelling studies.

Inspired from the important applications of spirocyclic compounds in medicinal chemistry, a new series of pyrazoline Spiro-oxindole tethered 1,2,3-triazole hybrids was reported via Cu(I)-catalyzed click reaction from isatin-pyrazoline linked terminal alkynes with in situ derived benzyl azides. Antimicrobial evaluation data showed that all hybrids exhibited promising efficacy towards the tested microbial strains. Antimicrobial screening as well as docking studies suggested that hybrid 6a was found to be most potent towards Aspergillus niger (MIC = 0.0122 μmol/mL) and Escherichia coli (MIC = 0.0061 μmol/mL). Molecular docking studies of 6a within the binding pockets of antibacterial and antifungal targets revealed good interactions with the binding energies of - 144.544 kcal/mol and - 154.364 kcal/mol against 1KZN (E. coli) and 3D3Z (A. niger), respectively. Further, MD simulations were performed to study the stability of the complexes formed at 300 K. Based on the RMSD trajectories, it is evident that 3D3Z-6a complex exhibits minimal deviation, whereas the 1KZN-6a complex displayed little more deviation compared to the protein but, both are in acceptable range. Moreover, 3D3Z-6a and 1KZN-6a showed maximum number of hydrogen bonds at 50 ns and 70 ns, respectively, thereby complementing the stability of these complexes.