Design, synthesis and anticancer activity of novel pyrimidine and pyrimidine-thiadiazole hybrid glycosides

• Published in: Nucleosides, nucleotides & nucleic acids Vol. 39; no. 7; pp. 1036 - 1056
• Main Authors: Khalaf, Hemat S., Tolan, Hala E. M., Radwan, Mohamed A. A., Mohamed, Ashraf M., Awad, Hanem M., El-Sayed, Wael A.
• Format: Journal Article
• Language: English
• Published: PHILADELPHIA Taylor & Francis 02.07.2020; Taylor & Francis Ltd
• Subjects: 1,2,3-triazole; 1,3,4-thiadiazole; Adenocarcinoma; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; Biochemistry & Molecular Biology; Breast cancer; Cell Line; Cell Proliferation - drug effects; Cell Survival - drug effects; click chemistry; Cytotoxicity; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Epithelial cells; Glycosides; Glycosides - chemical synthesis; Glycosides - chemistry; Glycosides - pharmacology; Glycosylation; Hep G2 Cells; HepG2; Humans; Life Sciences & Biomedicine; Liver cancer; MCF-7; MCF-7 Cells; Molecular Structure; NMR; Nuclear magnetic resonance; Pyrimidines; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Science & Technology; Structure-Activity Relationship; Thiadiazoles - chemistry; Thiadiazoles - pharmacology; Tumor cell lines; 1,3,4-THIADIAZOLES; MCF-7; click chemistry; MOLECULAR DOCKING; ANTIMALARIAL; glycosides; DISCOVERY; ALPHA-GLUCOSIDASE INHIBITORS; 1,2,3-TRIAZOLES; HepG2; 1,3,4-thiadiazole; BEARING; 1,2,3-triazole; DERIVATIVES; ANTIMICROBIAL ACTIVITY
• ISSN: 1525-7770; 1532-2335
• DOI: 10.1080/15257770.2020.1748649

New 1,3,4-thiadiazole thioglycosides linked to substituted pyrimidines were synthesized via glycosylation of 1,3,4-thiadiazole thiol compounds. Also, novel 1,2,3-triazole derivatives linked to carbohydrate units were prepared using the standard click chemistry conditions employing the Cu(I)-catalyzed azide-alkyne cycloaddition of substituted-aryl-azides with a selection of alkyne-functionalized sugars. The chemical structures of the new derivatives were verified using various spectroscopic techniques, such as IR, 1 H NMR, 13 C NMR and elemental analyses. The cytotoxic activities of the prepared compounds were investigated in vitro against human liver cancer (HepG-2) and human breast adenocarcinoma (MCF7) cell lines. In addition, the biological evaluation of the new compounds involved the investigation of their effects on a human normal retinal pigmented epithelial cell line (RPE1) using the MTT assay.