Piperonal-derived Schiff base molecules as potential multi-target therapeutic agents against Alzheimer's and diabetes

Ahmad A., Salar U., Özil M., Baltaş N., Tariq S. S., Ul-Haq Z., ...Daha Fazla

FUTURE MEDICINAL CHEMISTRY, cilt.17, sa.16, ss.1959-1975, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 17 Sayı: 16
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1080/17568919.2025.2549677
  • Dergi Adı: FUTURE MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.1959-1975
  • Recep Tayyip Erdoğan Üniversitesi Adresli: Evet

Özet

BackgroundThe dual burden of diabetes and Alzheimer's highlights the urgent need for multifunctional therapeutic agents. This study explores piperonal-derived Schiff base derivatives as potential dual-action enzyme inhibitors against alpha-amylase (AA), alpha-glucosidase (AG), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), offers a promising strategy for managing both conditions.MethodsSchiff base derivatives of piperonal (heliotropin) were synthesized, structurally characterized, and explored against established drug targets of diabetes mellitus (DM) and Alzheimer's disease (AD).ResultsCompounds 7 (IC50 = 5.73 +/- 0.01; 3.52 +/- 0.02 mu M) and 17 (IC50 = 10.91 +/- 0.02; 7.38 +/- 0.02 mu M) showed potent inhibitory effects against AG and AA enzymes, in comparison to acarbose (IC50 = 14.98 +/- 0.02 mu M; 14.64 +/- 0.02 mu M). However, analogs 7, 9, 10, 14, and 15, compounds 7 (IC50 = 2.92 +/- 0.02; 3.34 +/- 0.02 mu M) and 9 (IC50 = 8.16 +/- 0.03; 7.19 +/- 0.03 mu M) showed remarkable inhibitory results against AChE and BChE, respectively, compared to standard donepezil chloride (IC50 = 37.89 +/- 0.02 mu M; 41.56 +/- 0.03 mu M). Comprehensive kinetic analyses and molecular docking supported findings by in vitro studies. Synthesized derivatives were also checked for their antioxidant potential and demonstrated significant activity.ConclusionThese complementary studies highlight several hit candidates for further development as therapeutic agents against DM and AD.