Design, Synthesis, Characterization and Computational Studies of Mannich Bases Oxadiazole Derivatives as New Class of Jack Bean Urease Inhibitors

Abstract

Mannich bases consisting of 1,3,4‐oxadiazole‐2‐thione (3 a–3 l) bearing various substituents were synthesized and found potent jack bean urease inhibitors. The prepared compounds showed significantly good inhibitory activities with IC50 values from 9.45±0.05 to 267.42±0.23 μM. The compound 3 k containing 4‐chlorophenyl (−R) and 4‐hydroxyphenyl (−R′) was most active with IC50 9.45±0.05 μM followed by 3 e (IC50 22.52±0.15 μM) in which −R was phenyl and −R′ was isopropyl group. However, when both −R and −R′ were either 4‐chlorophenyl groups (3 l) or only −R′ was 4‐nitrophenyl (3 i), both compounds were found inactive. The detailed binding affinities of the produced compounds with protein were explored through molecular docking and data‐supported in‐vitro enzyme inhibition profiles. Drug likeness was confirmed by in silico ADME investigations and molecular orbital analysis (HOMO‐LUMO) and electrostatic potential maps were got from DFT calculations. ESP maps exposed that there are two potential binding sites with the most positive and most negative parts.

Biological Evaluation of Anti‐Cholinesterase Activity, in Silico Molecular Docking Studies, and DFT Calculations of Green Synthesized Thiadiazolo[3,2‐a]pyrimidine Derivatives

“…[5][6][7] On the other hand, heterocyclic compounds have been received much attention in the field of medicine and organic chemistry as a result of their extraordinary biological activity. [8][9][10][11][12] Especially, nitrogen-containing heterocycles are highly recognized in the field of anti-acetylcholinesterase compounds. [13,14] Among them, pyrimidine derivatives have been the focus of strong interest, due to their wide range of biological pharmacological profiles, including antibacterial, antiviral, anti-inflammatory, antioxidant, and antitumor activity.…”

“…On the other hand, heterocyclic compounds have been received much attention in the field of medicine and organic chemistry as a result of their extraordinary biological activity [8–12] . Especially, nitrogen‐containing heterocycles are highly recognized in the field of anti‐acetylcholinesterase compounds [13,14] .…”