Work

Synthetic approaches for novel fused pyrimidine derivatives: Design, structural characterization, antiviral, antitumor, and molecular docking evaluation

Year: 2024

Type: article

Abstract: The goal of this work was to synthesize new compounds for anticancer evaluation as a trial to obtain new antitumor agents with higher activity and fewer side effects. Therefore, the precursor 2,2'-(1,4-phenylenebis (thiazole-4,2-diyl))bis (3-(dimethylamino)acrylonitrile) (4) was used to synthesize various azolopyrimidine derivatives connected to the thiazole moiety. Compounds 5 – 11 , including pyrazolopyrimidine, triazolopyrimidine, and others, were produced by reacting enaminonitrile 4 with different N -nucleophiles. Additionally, compounds 12 – 15 , such as isoxazole and pyrimidinethione derivatives, were obtained by reacting compound 4 with guanidine, hydrazine hydrate, hydroxylamine hydrochloride, and thiourea. Enaminonitrile 4 was also treated with barbituric acid, isoxazolone, and pyrazolone to yield pyranopyrimidine derivatives 18 – 20 . Moreover, enaminonitrile 4 reacts with C -nucleophiles namely ''acetylacetone, dimedone, 2-cyanomethylbenzothiazole, and 2-cyanomethylbenzimidazole'' to give pyrano derivatives 21 , 22 and fused pyridone derivatives 23 and 24 , respectively. The cytotoxic activity of 20 novel compounds against HSV-1, HIV-1, and various cancer cell lines was assessed, with compounds 5 , 7 , and 9 showing the strongest effects. Molecular docking studies further evaluated the binding affinity of these derivatives, with docking scores ranging from −7.8679 to −8.3013 kcal/mol. Several new azolopyrimidine derivatives linked to the thiazole moiety were effectively synthesized and assessed in the study, and they showed notable cytotoxic activity against HSV-1, HIV-1, and several cancer cell lines.

Source: Heliyon

DOI: 10.1016/j.heliyon.2024.e40903