Nine new thiazole derivatives were synthesized considering 6-acetyl penicillanic acid (6-APA) and investigated for their antimicrobial activity. Ethyl 2-(2-mercaptoacetamido)-4-methylthiazole-5-carboxylate derivatives (3a–3i) were gained with a two-step synthetic method using conventional Hantzsch thiazole synthesis. The structural elucidation of the compounds was performed by ¹H-NMR, ¹³C-NMR spectral data and HRMS. All compounds were tested on eleven bacteria and sixteen fungi species and minimum inhibitory concentration (MIC) was determined for each. Compounds 3d (4-methyl-2-(2-((5-methyl-1,3,4-thiadiazol-2-yl), 3f (4-methyl-2-(2-((5-nitro-1H-benzimidazol-2-yl) and 3g (4-methyl-2-(2-((5-methyl-4H-1,2,4-triazol-3-yl) bearing thiazole, 5-nitrobenzimidazole and triazole rings respectively exhibited high antimicrobial activity against most of the strains. In silico physicochemical properties were calculated for the compounds and it was detected that they comply with the rules of drug availability. Graphical Abstract

This study examines the synthesis and evaluation of 11 newly developed compounds as potential anti‐Alzheimer's agents that occur via cholinesterase and β‐secretase inhibition. The compounds were tested for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using the modified Ellman method. The results showed that several compounds exhibited significant inhibition of AChE, particularly compounds 6d, 7a, and 7e, which demonstrated high inhibitory activity at lower concentrations, with IC₅₀ values of 0.120, 0.039, and 0.063 µM, respectively. However, the compounds showed limited effectiveness against BChE, with only a few compounds exhibiting moderate inhibition. Compound 7e showed an inhibitory effect against BACE‐1 close to that of the standard drug. Structural analysis revealed that the compounds with substituted benzothiazole and thiazole moieties exhibited the most promising inhibitory activity. This study provides valuable insights into the potential of these synthesized derivatives as a treatment against Alzheimer's disease. Moreover, the structure, stability, and properties of the active compounds were further investigated using density functional theory calculations. As a final note, the utilization of molecular docking and molecular dynamics simulation studies allowed us to elucidate the action mechanism of the active compounds and gain insights into the structure–activity relationship against AChE and β‐secretase proteins. These computational techniques provide valuable information on the binding modes, interactions with target enzymes, dynamic behavior, and conformational changes of the compounds, enabling a comprehensive understanding of their biological activity.

Today, chemotherapeutic agents are mostly used to fight cancer in clinics. But even though they have selectivity for cancer cells, their mechanism of action could result in necrosis. Therefore, we aimed to suggest new design strategies using a moderately active compound (MAC) to get better activity and increase the apoptotic effect in this study. Although MAC, previously synthesized and evaluated for its anticancer properties, has been marked as a moderately active compound, it has let us develop new molecules using its molecular core supported by molecular docking and molecular dynamics simulation. The caspase-3 enzyme was subjected to density functional theory (DFT), docking, and molecular dynamics simulation studies, and the results were analyzed to better understand the structure-activity relationship (SAR); thus, new design strategies were proposed.