Synthesis, <i>in Vitro</i> Cholinesterase Inhibition, Molecular Docking, DFT, and ADME Studies of Novel 1,3,4‐Oxadiazole‐2‐Thiol Derivatives

A new series of thieno nucleus embellished trinuclear (19, 20) and tetranuclear (21–24) nitrogen heteroaryl have been synthesized by the Suzuki cross‐coupling reaction using bis(triphenylphosphine)palladium(II) dichloride. All the synthesized compounds were characterized by IR, 1H‐NMR, 13CNMR and Mass spectral properties. In vitro antibacterial studies of the synthesized compound were conducted using broth microdilution assay employing Gram‐positive and Gram‐negative strains and half‐maximal inhibitory concentration (IC50) was determined. The result showed that compound 20 possess best antibacterial activity against S. aureus and E. coli with IC50 values of 60 μg mL−1 and 90 μg mL−1. Further to determine the mode of antibacterial action, compounds 20 and 21 were examined for in vitro bacterial dehydrogenase inhibitory assay. To understand the binding affinity of the synthesized compounds, the docking study was performed in the bacterial dehydrogenase enzyme by AutoDock Vina software and structure was confirmed by Discovery Studio Visualizer. All the synthesized compounds were docked in a good manner within the active sites of the bacterial dehydrogenase enzyme and exhibited good binding energies.

Section: Discussionmentioning

confidence: 99%

Section: Antibacterial Activity Determination Of Half-maximal Inhibit...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis and Theoretical Studies of Biologically Active Thieno Nucleus Incorporated Tri and Tetracyclic Nitrogen Containing Heterocyclics Scaffolds via Suzuki Cross‐Coupling Reaction

Sain

Jaiswal

Jain

et al. 2022

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

Mutahir

Khan

Almehizia

et al. 2023

Self Cite

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

Pouramiri,

Rashidi,

Lotfi

et al. 2023

A series of [1,3,4] thiadiazolo[3,2‐a]pyrimidine‐6‐carboxylate derivatives 4(a–n) have been designed and synthesized as inhibitors of acetylcholinesterase (AChE). Synthesizing of thiadiazolo[3,2‐a] pyrimidines was carried out in a single step, one‐pot reaction using aromatic aldehydes, ethyl acetoacetate and different derivatives of 1,3,4‐thiadiazoles (with molar ratio of 1:2:1 respectively) in conjunction with the catalyst, anhydrous iron(III) chloride by a grinding method under solvent‐free conditions at room temperature. The in‐vitro studies exhibited good potency for inhibiting AChE comparable with donepezil as the reference drug. The best results were obtained by Ethyl 2‐(4‐nitroophenyl)‐7‐methyl‐5‐(pyridin‐3‐yl)‐5H‐[1,3,4]thiadiazolo[3,2‐a]pyrimidine‐6‐carboxylate 4n with IC50 value of 0.082± 0.001 µM which was comparable with AChE inhibitory effects of donepezil (IC50 = 0.079 µM).