| Autor: |
Shirisha T; Department of Chemistry, National Institute of Technology, Warangal-506 004, India. kashinath@nitw.ac.in., Majhi S; Department of Chemistry, National Institute of Technology, Warangal-506 004, India. kashinath@nitw.ac.in., Divakar K; Department of Biotechnology, Sri Venkateswara College of Engineering (Autonomous), Sriperumbudur, Tamilnadu-602 117, India. divakar@svce.ac.in., Kashinath D; Department of Chemistry, National Institute of Technology, Warangal-506 004, India. kashinath@nitw.ac.in. |
| Jazyk: |
angličtina |
| Zdroj: |
Organic & biomolecular chemistry [Org Biomol Chem] 2024 Jan 24; Vol. 22 (4), pp. 790-804. Date of Electronic Publication: 2024 Jan 24. |
| DOI: |
10.1039/d3ob01760e |
| Abstrakt: |
A mild and greener protocol was developed for C-C (C(sp 3 )-H functionalization) and C-N bond formation to synthesize functionalized tacrine derivatives using a biodegradable and reusable deep eutectic solvent [(DES) formed from N , N '-dimethyl urea and L-(+)-tartaric acid in a 3 : 1 ratio at 80 °C]. The condensation of 9-chloro-1,2,3,4-tetrahydroacridines with a variety of aromatic aldehydes gave unsaturated compounds via C(sp 3 )-H functionalization (at the C-4 position) with good yields. The substituted N -aryl tacrine derivatives were obtained from the condensed products of 9-chloro-1,2,3,4-tetrahydroacridine with substituted anilines via the nucleophilic substitution reaction (SN 2 type) in the DES with good yields. This is the first example of C4-functionalized tacrine derivatives, highlighting the dual capacity of the DES to serve as both a catalyst and a solvent for facilitating C-N bond formation on acridine. The generated compounds were evaluated for acetyl/butyrylcholinesterase (AChE/BChE) and α-glucosidase inhibitory activity. It was found that the majority of the compounds reported here were significantly more potent inhibitors than the standard inhibitor tacrine (AChE IC 50 = 203.51 nM; BChE IC 50 = 204.01 nM). Among the compounds screened, 8m was found to be more potent with IC 50 = 125.06 nM and 119.68 nM towards AChE and BChE inhibition respectively. The α-glucosidase inhibitory activity of the compounds was tested using acarbose as a standard drug (IC 50 = 23 100 nM) and compound 8j was found to be active with IC 50 = 19 400 nM. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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