Development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for Alzheimer's treatment

Gupta S. M., Behera A., Jain N. K., Tripathi A., Rishipathak D., Singh S., ...Daha Fazla

RSC ADVANCES, cilt.13, sa.38, ss.26344-26356, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 13 Sayı: 38
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1039/d3ra03224h
  • Dergi Adı: RSC ADVANCES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, Chemical Abstracts Core, Compendex, Metadex, Directory of Open Access Journals
  • Sayfa Sayıları: ss.26344-26356
  • Erciyes Üniversitesi Adresli: Evet

Özet

Leading pathological markers of Alzheimer's disease (AD) include Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), Amyloid beta (A & beta;) and reactive oxygen species (ROS). Indole derivatives were identified and optimized to improve the potency against AChE, BuChE, A & beta; and ROS. The lead molecule IND-30 was found to be selective for AChE (selectivity ratio: 22.92) in comparison to BuChE and showed maximum inhibition potential for human AChE (IC50: 4.16 & PLUSMN; 0.063 & mu;M). IND-30 was found to be safe on the SH-SY5Y cell line until the dose of 30 mM. Further, molecule IND-30 was evaluated for its ability to inhibit AChE-induced A & beta; aggregation at 0.5, 10 and 20 & mu;M doses. Approximately, 50% of AChE-induced A & beta; aggregation was inhibited by IND-30. Thus, IND-30 was found to be multitargeting for AD. Leading pathological markers of Alzheimer's disease (AD) include Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), Amyloid beta (A & beta;) and reactive oxygen species (ROS).