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• A series of benzothiazol-1,3,4-oxadiazole-acetamide derivatives (7a – k) was synthesized and characterized. • Potent acetylcholinesterase (AChE) inhibitors were identified in 9 compounds. • Lineweaver-Burk plots were utilized to investigate the kinetic mechanism. • Cytotoxicity screening through MTT assay showed a good safety profile for most compounds. • Docking studies on the most active analogue and its interactions with the AChE active sites agreed with the experimental results. In this research, a series of benzothiazol-1,3,4-oxadiazole-acetamide derivatives (7a – k) were synthesized as potential therapeutic agents targeting Alzheimer's disease. The structures of the newly synthesized compounds were confirmed through spectral analyses, including FT-IR, 1HNMR , 13CNMR , and HRMS. These compounds exhibited excellent inhibitory potential against acetylcholinesterase (AChE), which compound 7i demonstrating remarkable activity (IC 50 = 0.08 ± 0.01 μM), surpassing the standard reference by 25-fold (IC 50 = 2.04 ± 0.05 μM). The Lineweaver–Burk plot indicated a competitive inhibition type for compound 7i. Additionally, cytotoxicity screening against human fibroblast HT1080 cells revealed a good safety profile for most compounds. Molecular docking studies on the most active compound (7i) further supported the experimental findings regarding its binding interactions with the active site of enzyme. [Display omitted] [ABSTRACT FROM AUTHOR]

• An efficient one-pot synthesis of dihydropyrimidinones was performed with cysteine as a bio-organic catalyst. • These compounds (4a – 4j) displayed significant in vitro urease inhibitory activity. • MTT assay was used to evaluate the cytotoxicity of all compounds in HT1080 human fibroblast cell lines. • The kinetic mechanism was investigated by Lineweaver-Burk plots. • In silico molecular docking studies supported the experimental results. The aim of the present research was to develop a one-pot, three-component method for the synthesis of some 3,4-dihydro pyrimidine-2-(1 H)-one (DHPM) derivatives using aldehydes, urea, and ethyl acetoacetate in the presence of cysteine as a green, bio-organic catalyst. This procedure has several key advantages, including a facile and convenient method, green and low-cost catalyst, high yield, short reaction time, and avoidance of the use of environmentally harmful solvents. It is important to note that the synthesized compounds (4a – j) were evaluated for in vitro urease inhibitory activity, and all were found to be more effective than the standard thiourea (IC 50 = 4.745 ± 0.054 µM), with urease inhibitory potentials between IC 50 = 0.058 ± 0.006 µM to 0.297 ± 0.066 µM. Lineweaver-Burk plots were used to study the kinetics of the most potent compound (4e), and the results showed that the compound non-competitively inhibited urease by forming an enzyme-inhibitor complex. In addition, HT1080 human fibroblast cell lines were used to test the toxicity of the synthesized compounds on cell viability using the MTT assay method, and all compounds except 4g, 4i, and 4j exhibited no significant toxic effects on cells even at high concentrations. Moreover, molecular docking was used to determine the binding interactions between the molecules (ligands) and the active site of the urease enzyme, and the ligands indicated acceptable binding energy values. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of 1,3,4-thiadiazol-1,3,4-oxadiazol-acetamide derivatives (7a – 7j) were synthesized as elastase inhibitors. • The in-vitro elastase inhibitory activity of all synthesized compounds was determined successfully. • The kinetic mechanism was investigated by Lineweaver-Burk plots. • MTT assay was used to evaluate the cytotoxicity of all compounds on B16F10 melanoma cell lines. • Molecular docking was applied to investigate the binding affinity of compounds with elastase and the ligands showed good binding energy values. Considering the biological significance of 1,3,4-thiadiazole/oxadiazole heterocyclic scaffolds, a novel series of 1,3,4-thiadiazole-1,3,4-oxadiazole-acetamide derivatives (7a – j) was designed and synthesized using molecular hybridization. The inhibitory effects of the target compounds on elastase were evaluated, and all of these molecules were found to be potent inhibitors compared to the standard reference oleanolic acid. Compound 7f exhibited the excellent inhibitory activity (IC 50 = 0.06 ± 0.02 μM), which is 214-fold more active than oleanolic acid (IC 50 = 12.84 ± 0.45 μM). Kinetic analysis was also performed on the most potent compound (7f) to determine the mode of binding with the target enzyme, and it was discovered that 7f inhibits the enzyme in a competitive manner. Furthermore, the MTT assay method was used to assess their toxicity on the viability of B16F10 melanoma cell lines, and all compounds did not display any toxic effect on the cells even at high concentrations. The molecular docking studies of all compounds also justified with their good docking score and among them, compound 7f had a good conformational state with hydrogen bond interactions within the receptor binding pocket, which is consistent with the experimental inhibition studies. [ABSTRACT FROM AUTHOR]