Synthesis, biological evaluation and molecular docking studies of novel 2-alkylthiopyrimidino-Tacrines as anticholinesterase agents and their DFT calculations

Publication date: Available online 14 February 2020Source: Journal of Molecular StructureAuthor(s): Chamseddine Derabli, Houssem Boulebd, Ahmed B. Abdelwahab, Celia Boucheraine, Sarah Zerrouki, Chawki Bensouici, Gilbert Kirsch, Raouf Boulcina, Abdelmadjid DebacheAbstractTo search for effective and selective inhibitors of cholinesterases (AChE and BuChE), a series of poly-functionalized Tacrine-derived compounds specifically 2-(alkylthio)-4-aryl-6,7,8,9-tetrahydropyrimido[4,5-b]quinolin-5-amines were designed an synthesized via Friedlander reaction. The structures of the newly synthesized compounds were confirmed on the basis of their spectral data (1H NMR, 13C NMR) and elemental analyses (CHNS). Compounds 3a-h were evaluated for their abilities to inhibit AChE and BChE. The obtained biological results revealed that some synthesized compounds displayed higher anti-cholinesterase activity in comparison to Galantamine. Among them, compound 3d bearing S-ethyl and 4-chlorophenyl moieties showed the most potent activity against AChE/BuChE with IC50s values of 4,32 and 15,10 μM, respectively. The anti-AChE activity of 3d was 5-fold more than that of reference drug Galantamine. Moreover, molecular docking studies were performed for the most active derivatives, 3d and 3c, in which binding mode between these compounds and the receptors were determined. Density functional theory (DFT) method at B3LYP/6-311++G (d,p) level of theory was employed to gain insights into the molecular struct...
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research