Molecular structure, spectroscopy, reactivity and biological activity: A collection of selected communications based on thiadiazole linked benzamide derivatives

Alzheimer's disease (AD), the most common class of dementia was targeted in the current research work by efficiently synthesizing novel series of heterocyclic thiadiazole based benzamide derivatives (1–16). Molecular structure of all the novel compounds was confirmed via spectroscopic analytical spectroscopic techniques NMR (¹H and ¹³C) and HREI-MS. The biological profile of these compounds mainly depends on their molecular structure (substitution pattern). Inhibitory potential of these compounds was compared under in-vitro investigation with the biological profile of standard compound donepezil with IC₅₀=7.30 ±0.10 and 8.70 ±0.20 for AChE and BuChE respectively. In this analogy, analogue 4 with para CF₃ emerged as the excellent inhibitor with captivating potential of IC₅₀ of 3.20 ±0.10 and 4.30 ±0.20 µM. Validation of the biological profile was conducted under in-silico molecular docking study which provided insight into the binding interactions of potent ligands with target enzymes. Different interactions including hydrogen bonding were found as the key factors in inhibition of enzymes. Moreover, the pharmacokinetic analysis of the potent compounds provided the compelling drug potential against Alzheimer's disease.