Synthesis, anticancer activity and molecular docking of new triazolo[4, 5-d]pyrimidines based thienopyrimidine system and their derived N-glycosides and thioglycosides. (2nd November 2021)

• Record Type: Journal Article
• Authors: Khattab, Reham R.; Hassan, Allam A.; A. Osman, Dalia A.; Abdel-Megeid, Farouk M.; Awad, Hanem M.; Nossier, Eman S.; El-Sayed, Wael A.
• Is Part Of: Nucleosides, nucleotides & nucleic acids. Volume 40:Number 11(2021)
• Page Start: 1090
• Page End: 1113
• Publication Date: 2021-11-02
• Subjects: Triazolopyrimidine -- thienopyrimidine -- glycosides -- thioglycosides -- anticancer -- HepG-2 -- MCF-7 -- EGFR; Nucleosides -- Periodicals; Nucleotides -- Periodicals; Nucleic acids -- Periodicals; 572.8
• DOI: 10.1080/15257770.2021.1975297
• Languages: English
• ISSNs: 1525-7770

Abstract

Abstract: A series of new substituted triazolo[4, 5- d ]pyrimidine derivatives linked to thienopyrimidine ring system were prepared as a hybrid heterocyclic systems, as possible nucleobases analogs, starting from the key carboxamide derivative 2 and its azide precursor via heterocyclization reactions and their structures were characterized. Glycosylation of the prepared triazolopyrimidine derivatives was performed and afforded, regioselctively, the corresponding thienopyrimidine-triazolopyrimidine hybrid N 1 -glycosides and their thioglycoside analogues in good yields. The synthesized glycosyl heterocycles were studied for their cytotoxic activity against HepG-2 and MCF-7 human cancer cells and significant results were obtained. Compounds 7a, 8 b, 9 b, 9a and 7 b demonstrated promising activities comparable to the activity of the doxorubicin for (HepG-2) cell line. Furthermore, a number of the afforded triazolopyrimidine glycosides were found potent against cancer cells (MCF-7). Furthermore, docking simulation the promising thienopyrimidine analogues 7-13 was done against EGFR kinase to provide a binding model that could serve in discovery of further anticancer agents.