Chalcone derivatives have attracted considerable research interest due to their potential antimicrobial, antifungal, and insecticidal activities. The present study aimed to synthesize chalcone derivatives and evaluate their antimicrobial activity using in vitro methods, supported by molecular docking studies. All solvents were redistilled before use, and reaction progress was monitored by thin-layer chromatography (TLC), with spots visualized under ultraviolet light or iodine vapour. The synthesized compounds were purified by recrystallization, and their melting points were determined using the open-capillary method. During synthesis, finely powdered zinc chloride (8.25 g) was dissolved in glacial acetic acid (18 mL) by heating, followed by the addition of dry resorcinol (approximately 5.5 g) with continuous stirring. The reaction mixture was maintained at elevated temperatures under the specified experimental conditions. The antimicrobial activity of compounds C1–C6 was evaluated against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli using the cup-plate method. Dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) were used as controls. The results indicated that compounds C3 and C4 exhibited promising antibacterial activity, approaching that of the standard compound amoxicillin. Molecular docking studies revealed that compound C1 showed the maximum negative contribution, with a score of −8.03006, whereas compound C6 exhibited the lowest negative contribution, at −7.71101. These findings suggest that the synthesized derivatives may serve as promising candidates for further antimicrobial investigation.

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis are biologically diverse disorders associated with progressive neuronal dysfunction. In several of these conditions, abnormal handling or accumulation of proteins contributes to disease pathology. Conventional small-molecule inhibitors generally reduce a protein’s activity while leaving the protein itself present. Targeted protein degradation (TPD) offers a complementary approach: it aims to recruit a selected protein to cellular disposal pathways and lower its abundance. Major strategies include proteolysis-targeting chimeras (PROTACs), molecular glue degraders and autophagy-based systems such as AUTACs and ATTECs. These platforms have produced encouraging proof-of-concept results against targets relevant to neurodegeneration, including tau and mutant huntingtin, but evidence remains predominantly preclinical. Translating TPD into central nervous system (CNS) medicines requires adequate blood–brain barrier penetration, cell-specific exposure, productive target engagement, selective degradation and long-term safety. Computational tools—including structure analysis, docking, molecular dynamics, physicochemical profiling and ADMET prediction—can support early prioritisation, but they cannot establish degradation or clinical efficacy by themselves. This narrative review summarizes the biological basis of TPD, major degrader formats, selected disease applications, in silico evaluation strategies and the principal translational barriers. The central conclusion is that TPD is a promising research strategy rather than an established treatment for neurodegenerative diseases; experimental validation and careful CNS pharmacology remain essential.