Synthesis,Biological Evaluation,and In Silico Studies of New Acetylcholinesterase Inhibitors Based on Quinoxaline Scaffold

A quinoxaline scaffold exhibits various bioactivities in pharmacotherapeutic interests. In this research, twelve quinoxaline derivatives were synthesized and evaluated as new acetylcholinesterase inhibitors. We found all compounds showed potent inhibitory activity against acetylcholinesterase (AChE) with IC₅₀ values of 0.077 to 50.080 µM, along with promising predicted drug-likeness and blood–brain barrier (BBB) permeation. In addition, potent butyrylcholinesterase (BChE) inhibitory activity with IC₅₀ values of 14.91 to 60.95 µM was observed in some compounds. Enzyme kinetic study revealed the most potent compound (6c) as a mixed-type AChE inhibitor. No cytotoxicity from the quinoxaline derivatives was noticed in the human neuroblastoma cell line (SHSY5Y). In silico study suggested the compounds preferred the peripheral anionic site (PAS) to the catalytic anionic site (CAS), which was different from AChE inhibitors (tacrine and galanthamine). We had proposed the molecular design guided for quinoxaline derivatives targeting the PAS site. Therefore, the quinoxaline derivatives could offer the lead for the newly developed candidate as potential acetylcholinesterase inhibitors.     

A Shear-Thinning,Self-Healing,Dual-Cross Linked Hydrogel Based on Gelatin/Vanillin/Fe3+/AGP-AgNPs: Synthesis,Antibacterial, and Wound-Healing Assessment

A shear-thinning and self-healing hydrogel based on a gelatin biopolymer is synthesized using vanillin and Fe³⁺ as dual crosslinking agents. Rheological studies indicate the formation of a strong gel found to be injectable and exhibit rapid self-healing (within 10 min). The hydrogels also exhibited a high degree of swelling, suggesting potential as wound dressings since the absorption of large amounts of wound exudate, and optimum moisture levels, lead to accelerated wound healing. Andrographolide, an anti-inflammatory natural product is used to fabricate silver nanoparticles, which are characterized and composited with the fabricated hydrogels to imbue them with anti-microbial activity. The nanoparticle/hydrogel composites exhibit activity against Escherichia coli, Staphylococcus aureus, and Burkholderia pseudomallei, the pathogen that causes melioidosis, a serious but neglected disease affecting southeast Asia and northern Australia. Finally, the nanoparticle/hydrogel composites are shown to enhance wound closure in animal models compared to the hydrogel alone, confirming that these hydrogel composites hold great potential in the biomedical field.