Background: Alzheimer’s disease (AD) is largely linked with oxidative stress, the accumulation of amyloid-β plaques, and hyperphosphorylated τ-protein aggregation. Alterations in dopaminergic and serotonergic neurotransmission have also been implicated in various AD-related symptoms. Methods: To explore new therapeutic agents, a series of bicyclic and tricyclic thieno-oxazepine derivatives were synthesized as potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The resultant compounds were purified via HPLC and characterized using spectral analysis techniques. Histopathological examinations, other antioxidants, and anti-inflammatory biomarkers were evaluated, and in silico ADMET calculations were performed for synthetic hybrids. Molecular docking was utilized to validate the new drugs’ binding mechanisms. Results: The most powerful AChE inhibitors were 14 and 16, with respective values of IC₅₀ equal to 0.39 and 0.76 µM. Derivative 15 demonstrated remarkable BChE-inhibitory efficacy, on par with tacrine, with IC₅₀ values of 0.70 µM. Hybrids 13 and 15 showed greater selectivity towards BChE, despite substantial inhibition of AChE. Compounds 13 and 15 reduced escape latency and raised residence time, with almost equal activity to donepezil. Conclusions: According to these findings, the designed hybrids constitute multipotent lead compounds that could be used in the creation of novel anti-AD medications.

In order to lessen the severity of infectious diseases, anti-infective agents—drugs that prevent, combat, or control infections brought on by microorganisms—are essential in contemporary medicine. To tackle antimicrobial resistance, this project intends to design and synthesize hybrid compounds that contain pyrrolidine, quinoxaline and a hydrazinyl bridge, and assess the antimicrobial and antifungal properties of these compounds against a variety of pathogenic strains. The bactericidal properties of hybrids 24, 27, and 29 against E. coli were verified. The MIC of 12.5 µM was shown by hybrids 24, 25, and 31, which suggests bactericidal hybrids are effective against P. aeruginosa at greater concentrations. In comparison to Levofloxacin, treatment with all hybrids produced an 89–92% reduction in biofilm formation at 90% MIC. Eight hybrids' killing kinetics against P. aeruginosa were time-dependent, with an abrupt decrease in CFU number observed at higher concentrations. While 4-fold and 8-fold MICs resulted in nearly total bacterial eradication, primary bacterial elimination happened after three hours. The most effective DNA gyrase inhibitors were hybrids 25, 28, and 31; their IC₅₀ values were significantly less than that of ciprofloxacin (77.3, 87.6, and 65.5 µM, respectively). To determine the best drug-like qualities, the study examined the physicochemical and pharmacokinetic features of active compounds. Molecular docking simulation experiments were also conducted to comprehend the binding interactions and mechanisms of action of these hits.