Medicinal perspectives, molecular docking and structure activity relationship of benzothiazole derived thiazole-based bis-benzohydrazide as potential anti-Alzheimer agents

• This study presents a novel route for the synthesis of benzothiazole derived thiazole based bis - benzohydrazide derivatives. • These derivatives were biological investigated for their anti-Alzheimer’s potential. • The structural confirmation of the synthesized compounds was achieved via spectroscopic analysis. • These derivatives were subjected to in silico molecular docking study to gain insight into the binding interactions with target enzymes. • These derivatives were also investigated for their pharmacokinetic properties through ADME analysis to study their drug likeness attributes. A new series of benzothiazole derived thiazole-based bis -benzohydrazide hybrid (1–20) analogs were synthesized. Initially, the product confirmation was identified by employing TLC and the basic skeleton of the new hybrid synthesized compounds was further confirmed through spectroscopic techniques such as 13 CNMR, 1 HNMR and HREI-MS. Moreover, the synthesized analogs were tested for their inhibitory activities against acetylcholinesterase and butyrylcholinesterase. In the whole series, compounds 1 , 2, 3 and 6 were found with potent activity against acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE). Molecular docking inveatigation of the potent compounds was performed within the active site of acetylcholinesterase and butyrylcholinesterase revealing compounds 1 , 2, 3 and 6 showing promising binding orientations against both enzymes as compared to reference drug donepezil with their IC 50 values 1 ( 2.20 ± 1.40 and 3.18 ± 0.45 μM ), 2 ( 2.89 ± 1.25 and 2.78 ± 1.49 μM ), 3 ( 2.94 ± 1.10 and 3.07 ± 1.23 μM ), 6 ( 5.83 ± 1.45 and 6.03 ± 3.08 μM ), respectively, and reference drug (IC 50 = 8.73 ± 2.68 and 9.30 ± 2.60 μM for acetylcholinesterase and butyrylchlinesterase, respectively. In addition, ADME studies were conducted to gain a deeper understanding of the functional mechanisms of a drug on a living organism. It is considered that benzothiazole derived thiazole based bis -benzohydrazide hybrid analogs (1, 2, 3, 6) might be better inhibitors of acetylcholinesterase and butyrylcholinesterase enzymes.