New oxadiazole bearing thiosemicarbazide analogues: Synthesis, anti-alzheimer inhibitory potential and their molecular docking study

Synthesized oxadiazole-bearing thiosemicarbazide analogues (1–14) were characterized by NMR and HR-EIMS and were tested against acetylcholinesterase and butyrylcholinesterase activities. All analogues showed an excellent acetylcholinesterase activity with IC50 value ranging between 2.12 ± 0.23 to 103.41 ± 0.16 µM (Standard eserine IC50 = 0.85 ± 0.0001 µM) and butyrylcholinesterase activity ranging IC50 values between 1.13 ± 0.11 to 109.20 ± 0.12 µM (Standard Eserine IC50 = 0.04 ± 0.0001 µM) respectively. Analogue 14 was most potent acetylcholinesterase inhibitor with an IC50 value of 2.12 ± 0.23 µM while analogue 11 was most active butyrylcholinesterase inhibitor with an IC50 value of 1.13 ± 0.11 µM. Structure-activity relationship was established which mainly depends upon number, nature and position of substituent/s on phenyl ring ‘A’. Binding interaction of most potent analogues was confirmed through molecular docking studies. Mode of synthesis through which our products were synthesized is hydrazide, oxadiazole ring and thiosemicarbazide formation. [Display omitted]