Design, synthesis and anticancer evaluation of novel pyrazole, pyrazolo[3,4-d]pyrimidine and their glycoside derivatives.
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.
a Faculty of Specific Education, Ain Shams University , Abassia , Cairo , Egypt.
Ibrahim F
IF
Nassar
b Department of Chemistry , Faculty of Science, Zagazig University , Zagazig , Egypt.
Ahmed F
AF
El Farargy
c Department of Chemistry , Faculty of Science, Cairo University , Giza , Egypt.
Fathy M
FM
Abdelrazek
d Pharmaceutical Chemistry Department , Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University , Cairo , Egypt.
Nasser S M
NSM
Ismail
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D051357:Cyclin-Dependent Kinase 2 / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D006027:Glycosides / Q000737:chemistry*; D006801:Humans; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D000970:Antineoplastic Agents; D006027:Glycosides; D011720:Pyrazoles; D011743:Pyrimidines; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
Pyrazole; pyrazolopyrimidine; cytotoxicity study; molecular modeling