Synthesis, Spectral Analysis, Physicochemical, and Biological Potential of Unexplored Novel Indole Tethered Thiazolo[2,3‐c][1,2,4]Triazoles by DFT and Molecular Docking Insights

Abstract

We here in report the molecular structures of 5‐(5‐substituted‐1 H ‐indol‐3‐yl)‐3‐(4‐substituted‐phenyl)thiazolo[2,3‐c][1,2,4]triazoles 5(a‐l) and their biological activities. Newly synthesized compounds were characterized through FTIR, 1 H & 1 3 C‐NMR and mass spectroscopy. DFT analysis at the B3LYP/6‐311G+(d,p) level provided insights into frontier molecular orbitals, and molecular electrostatic potential. In vitro cyclooxygenase , acetylcholinesterase , ( AChE ) and butyrylcholinesterase ( BChE ) inhibition activities were evaluated for the foresaid synthesized compounds. Amongst, the experimental values were displayed that the compounds 5a, 5d, and 5e were revealed that good COX‐1 inhibitory effect with IC 50 value 2.05, 1.89 and 1.95 µM respectively. Amongst all the synthesized derivatives, the precursor compound 3a, showed good inhibitory activity against AChE and BChE with IC 50 values of 05.52 ± 0.22 and 8.22 ± 0.42 µM respectively. Further, the drug likeness predictions were investigated for the all the compounds. Finally, in silico molecular modelling studies were evaluated for the synthesized compounds against the protein's cyclooxygenase ‐1 (PDB id: 3N8V), cyclooxygenase ‐2 (PDB id: 6COX), acetylcholinesterase (PDB ID: 7E3H) and butyrylcholinesterase (PDB ID: 4BDS).