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

Autor:	Sefrji FO; Department of Biology, College of Science, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia., Alrefaei AF; Department of Biology/Genetic and Molecular Biology Central Laboratory (GMCL), Jamoum University College, Umm Al-Qura University, Makkah, 2203, Saudi Arabia., Imam MA; Department of Medical Microbiology and Parasitology, Qunfudah Faculty of Medicine, Umm Al-Qura University, Al-Qunfudah, 21961, Saudi Arabia., Ashour GRS; Department of Chemistry, College of Science, Umm Al-Qura University, Makkah, 24230, Saudi Arabia., Abualnaja MM; Department of Chemistry, College of Science, Umm Al-Qura University, Makkah, 24230, Saudi Arabia., Attar RMS; Department of biological sciences/ Microbiology, Faculty of Science, University of Jeddah, Jeddah, 21959, Saudi Arabia., Darwish AAA; Advanced Materials Research Laboratory, Department of Physics, Faculty of Science, University of Tabuk, Tabuk, 71491, Saudi Arabia., El-Metwaly NM; Department of Biology, College of Science, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia.; Department of Chemistry, Faculty of Science, Mansoura University, El-Gomhoria Street, 35516, Egypt.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Dec 04; Vol. 10 (24), pp. e40903. Date of Electronic Publication: 2024 Dec 04 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e40903
Abstrakt:	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. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 Published by Elsevier Ltd.)
Databáze:	MEDLINE
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