A novel class of thiazole based thiadiazole hybrids: The privileged scaffolds of potent anti-Alzheimer's activity along with molecular docking and ADME analysis

A novel series of thiazole-thiadiazole based schiff base derivatives (1-16) were synthesized and examined for their inhibitory profile against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). All the compounds exhibited excellent inhibitory activity ranging from IC50= 1.87 f 1.47 to 27.4 f 2.45 mu M for AChE and 1.72 f 1.43 to 29.4 f 1.87 mu M for BuChE when compared with the standard drug donepezil (IC50= 3.87 f 1.14 mu M and 3.56 f 2.52 mu M for AChE and BuChE, respectively). Among the members of the whole series, compounds-6 (IC50 = 3.49 f 1.20 mu M, 3.18 f 0.27 mu M), 7 (IC50 = 3.20 f 1.14 mu M, 3.21 f 0.49 mu M), 8 (IC50 =1.87 f 1.47 mu M, IC50 = 1.72 f 1.43) and 9 (IC50 = 2.18 f 1.02 mu M, IC50 = 2.02 f 0.49 mu M), showed remarkable potency against AChE and BuChE and emerged as anti-alzheimer's agents. Molecular docking study revealed the excellent binding interactions of ligands with different amino acids of the target enzymes. Structure activity relationship (SAR) study was also conducted to evaluate inhibitory potency of all the derivatives that depends on the position, number and nature of the substituents. Furthermore, ADME outcomes authenticate the drug likeness of the potent analogs. Structural confirmation of the derivatives was achieved through different spectroscopic techniques, including 13C NMR, 1H NMR and HREI-MS.