Design, synthesis and anticancer evaluation of novel pyrazole, pyrazolo[3,4-d]pyrimidine and their glycoside derivatives

ABSTRACT

The chalcone derivatives 3a,b were cyclized upon reaction with thiourea to give the pyrazolo[3,4-d]pyrimidine derivatives 5a,b. Condensation of 5a,b and their hydrazide derivatives 8a,b with cyclic and acyclic glucose gave the condensed S- and N-glycosides 7a,b and 9a,b, respectively. Reaction of 3b with ethyl cyanoacetate followed by reaction with cyclic glucose afforded a mixture of the O- and/or N-glycoside isomers 12 and 13, respectively. The pyrazolo[3,4-c]pyrazole derivative 14 was also obtained from the reaction of 3b with hydrazine hydrate. A number of the synthesized compounds were screened for their antitumor activity against three different tumor cell lines HEPG2 (liver), HCT116 (colon) and MCF-7 (breast) with a docking study against CDK2.

KEYWORDS:

• Pyrazole; pyrazolopyrimidine
• cytotoxicity study
• molecular modeling

Acknowledgments

F.M. Abdelrazek thanks the Alexander von Humboldt-Foundation (Germany) for granting a short research fellowship (July–September 2015) and for the continuous help and support. Thanks are also due to Professor Peter Metz, Institute of Organic Chemistry, TU Dresden for his repeated invitations and generous hospitality.