Design, Synthesis and Anticancer Activity of New Thiazole-Tetrazole or Triazole Hybrid Glycosides Targeting CDK-2 via Structure-Based Virtual Screening.
BACKGROUND & OBJECTIVE
The target tetrazole glycosides were synthesized by construction of ring system by cycloaddition reaction of benzothiazole-linked nitrile derivative and sodium azide followed by N-glycosylation process and deprotection.


METHODS
The triazole glycosides were prepared by applying click approach involving dipolar cycloaddition of benzothiazole possessing alkyne functionality and different glycosyl azides. The products incorporating acyclic analogs of sugar moieties were synthesized through alkylation using acyclic oxygenated halides.


RESULTS
The anticancer activity was studied against human breast adenocarcinoma cells (MCF-7) and human normal Retina pigmented epithelium cells (RPE-1). High activities were revealed by three compounds with IC50 values 11.9-16.5 µM compared to doxorubicin (18.6 µM) in addition to other four derivatives with good inhibition activities.


CONCLUSION
Enzyme docking investigation was performed into cyclin-dependent kinase 2 (CDK2); a potential target for cancer medication. Compounds which have possessed highest activities revealed good fitting inside the binding site of the protein molecular surface and showed minimum binding energy.
['Kassem|Asmaa F|AF|', 'Abbas|Eman M H|EMH|', 'El-Kady|Dina S|DS|', 'Awad|Hanem M|HM|', 'El-Sayed|Wael A|WA|']
D000970:Antineoplastic Agents D001393:Azoles D001665:Binding Sites D020134:Catalytic Domain D002460:Cell Line D002470:Cell Survival D051357:Cyclin-Dependent Kinase 2 D015195:Drug Design D006027:Glycosides D006801:Humans D020128:Inhibitory Concentration 50 D062105:Molecular Docking Simulation D013777:Tetrazoles D013844:Thiazoles D014230:Triazoles
glycosides CDK-2 docking 1,2,3-triazoles Thiazole breast cancer tetrazoles.