Novel Bis-Sulfonate Schiff Base Derivatives as Dual AChE Inhibitors and Antimicrobial Agents: Synthesis and Molecular Docking Studies
RUSSIAN JOURNAL OF GENERAL CHEMISTRY, cilt.96, sa.7, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 96 Sayı: 7
- Basım Tarihi: 2026
- Doi Numarası: 10.1134/s1070363225608506
- Dergi Adı: RUSSIAN JOURNAL OF GENERAL CHEMISTRY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Academic Search Ultimate (EBSCO), Materials Science & Engineering Collection (ProQuest), Technology Collection (ProQuest)
- Karadeniz Teknik Üniversitesi Adresli: Evet
Özet
A series of bis-sulfonate Schiff base derivatives were synthesized by the condensation of substituted 4-formylphenyl benzenesulfonates with 1,5-diaminopentane. The resulting products were obtained in high purity and fully characterized by IR, 1H and 13C NMR analyses, followed by molecular docking and molecular dynamics studies. The compounds were evaluated for their antimicrobial and acetylcholinesterase (AChE) inhibitory activities, revealing a clear substituent-dependent structure-activity relationship. Among them, {[pentane-1,5-diylbis(azanylylidene)]bis(methanylylidene)}bis(4,1-phenylene)bis(4-nitrobenzenesulfonate), bearing a nitro group, showed the most potent AChE inhibition (IC50 = 0.3 & micro;M), comparable to galantamine (0.4 & micro;M), and exhibited broad-spectrum antimicrobial activity (MIC = 156-625 & micro;g/mL). {[Pentane-1,5-diylbis(azanylylidene)]bis(methanylylidene)}bis(4,1-phenylene)bis(4-chlorobenzenesulfonate) and {[pentane-1,5-diylbis(azanylylidene)]bis(methanylylidene)}bis(4,1-phenylene)bis(4-fluorobenzenesulfonate) presented notable AChE inhibition, while electron-donating substituents decreased activity. Structure-based docking, 100 ns all-atom molecular dynamics simulations, and MM/PBSA free-energy calculations consistently supported {[pentane-1,5-diylbis(azanylylidene)]bis(methanylylidene)}bis(4,1-phenylene) bis(4-nitrobenzenesulfonate) as the most promising inhibitor, displaying a stable binding mode within the catalytic and peripheral anionic sites and a favorable binding free energy (Delta Gbind = -38.02 kcal/mol). Overall, these findings identify {[pentane-1,5-diylbis(azanylylidene)]bis(methanylylidene)}bis(4,1-phenylene)bis(4-nitrobenzenesulfonate) as a dual-active lead molecule and provide valuable insights for the rational design of next-generation AChE inhibitors and antimicrobial agents.