Synthesis, chemical characterization, and anti-proliferative action of 1,2,4-triazole N-glycoside derivatives

Tolan, Hala E.M.; Fahim, Asmaa M; Ismael, Eman H.I.

doi:10.21608/ejchem.2023.217561.8139

Synthesis, chemical characterization, and anti-proliferative action of 1,2,4-triazole N-glycoside derivatives

Document Type : Original Article

Authors

¹ Department of Photochemistry, National Research Centre, Dokki, P.O. Box.12622, Cairo, Egypt.

² Department of Green Chemistry, National Research Center, Cairo, Egypt

³ Department of Organometallic and Organometalloid Chemistry, National ResearchCentre, Dokki, P.O. Box.12622, Cairo, Egypt.

10.21608/ejchem.2023.217561.8139

Abstract

In this study, we have reacted the mercapto-N-phenyl-1,2,4-triazolothiazolo derivative 1a with acetylated bromo galactose 2a to give the new O-acetylated N-phenyl-1,2,4-triazolo thiazolotetrahydropyrane thioglycoside derivative 3a in a good yield. Treatment of the acetylated thioglycoside derivative 3a with ammonia solution in methanol resulted in de-acetylation where the corresponding free hydroxyl-tetrahydropyrane thioglycoside derivative 4a has been formed. Similarly, reaction of the -N-amino-1,2,4- triazolothiazolo derivative 1b with a five-membered ring glycoside derivative ,namely, acetylated bromo ribose 2b gave the corresponding new O-acetylated N-amino-1,2,4-triazolothiazolo- tetrahydrofurane thioglycoside derivative 3b. Hydrolysis of compound 3b with ammonia in methanol yielded the corresponding free hydroxyltetrahydrofurane thioglycoside derivative 4b. Structures of the new products were elucidated with compatible micro analytical and spectroscopic (FT-IR, 1H-NMR, 13C-NMR ) measurements. The new synthesized 1,2,4-triazole glycoside derivatives 3a,b and 4a,b were found to exhibit anticancer activity in vitro against a number of human cancer cell lines, including MCF-7 and HCT-116. The structural analysis of the KSHV thymidylate synthase (PDB ID: 5h38) and the crystal structure of the Ternary Complex of KRIT1 bound to the Rap1 GTPase and the Heart of Glass (HEG1) cytoplasmic tail (PDB ID: 4hdq) were both used to determine the potential interactions of glycosyl triazoles. Additionally, the 1,2,4-triazole N-glycosides 3a, 3b, 4a, and 4b were proven to be stable by employing the DFT/B3LYP/6-31G(d) basis set to explore and determine the physical descriptors of the existence of the acetyl and hydroxy groups of the glycoside ring using FMO.

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