| Title : Metal-free synthesis of functionalized tacrine derivatives and their evaluation for acetyl\/butyrylcholinesterase and alpha-glucosidase inhibition - Shirisha_2024_Org.Biomol.Chem__ |
| Author(s) : Shirisha T , Majhi S , Divakar K , Kashinath D |
| Ref : Org Biomol Chem , : , 2024 |
| Abstract : 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 degreesC]. 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 alpha-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 alpha-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. |
| ESTHER : Shirisha_2024_Org.Biomol.Chem__ |
| PubMedSearch : Shirisha_2024_Org.Biomol.Chem__ |
| PubMedID: 38167698 |
Shirisha T, Majhi S, Divakar K, Kashinath D (2024)
Metal-free synthesis of functionalized tacrine derivatives and their evaluation for acetyl\/butyrylcholinesterase and alpha-glucosidase inhibition
Org Biomol Chem
:
Shirisha T, Majhi S, Divakar K, Kashinath D (2024)
Org Biomol Chem
: