Development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for Alzheimer's treatment
RSC ADVANCES, cilt.13, sa.38, ss.26344-26356, 2023 (SCI-Expanded, Scopus)
- 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).