Synthesis of new <i>N</i>-(5,6-methylenedioxybenzothiazole-2-yl)-2-[(substituted)thio/piperazine]acetamide/propanamide derivatives and evaluation of their AChE, BChE, and BACE-1 inhibitory activities

Tutus B., Kaya A. Z., Baz Y., Evren A. E., SAĞLIK ÖZKAN B. N., YURTTAŞ L.

DRUG DEVELOPMENT RESEARCH, cilt.85, sa.4, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 85 Sayı: 4
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1002/ddr.22214
  • Dergi Adı: DRUG DEVELOPMENT RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, Veterinary Science Database
  • Anadolu Üniversitesi Adresli: Evet

Özet

In this study, the synthesis of N-(5,6-methylenedioxybenzothiazole-2-yl)-2-[(substituted)thio/piperazine]acetamide/propanamide derivatives (3a-3k) and to investigate their acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and beta-secretase 1 (BACE-1) inhibition activity were aimed. Mass, H-1 NMR, and C-13 NMR spectra were utilized to determine the structure of the synthesized compounds. Compounds 3b, 3c, 3f, and 3j showed AChE inhibitory activity which compound 3c (IC50 = 0.030 +/- 0.001 mu M) showed AChE inhibitory activity as high as the reference drug donepezil (IC50 = 0.0201 +/- 0.0010 mu M). Conversely, none of the compounds showed BChE activity. Compounds 3c and 3j showed the highest BACE-1 inhibitory activity and IC50 value was found as 0.119 +/- 0.004 mu M for compound 3j whereas IC50 value was 0.110 +/- 0.005 mu M for donepezil, which is one of the reference substance. Molecular docking studies have been carried out using the data retrieved from the server of the Protein Data Bank (PDBID: 4EY7 and 2ZJM). Using in silico approach behavior active compounds (3c and 3j) and their binding modes clarified.