Design, synthesis and antiproliferative evaluation of novel pyrazolo-pyrimidine derivatives with expected cyclin-dependent kinase 2 inhibitory effect
Younes, A., Shawer, T., El-Sehrawi, H. (2022). Design, synthesis and antiproliferative evaluation of novel pyrazolo-pyrimidine derivatives with expected cyclin-dependent kinase 2 inhibitory effect. EKB Journal Management System, 2(2), 9-20. doi: 10.21608/aijpms.2022.77353.1075
Amal S Younes; Taghreed Z Shawer; Hend MA El-Sehrawi. "Design, synthesis and antiproliferative evaluation of novel pyrazolo-pyrimidine derivatives with expected cyclin-dependent kinase 2 inhibitory effect". EKB Journal Management System, 2, 2, 2022, 9-20. doi: 10.21608/aijpms.2022.77353.1075
Younes, A., Shawer, T., El-Sehrawi, H. (2022). 'Design, synthesis and antiproliferative evaluation of novel pyrazolo-pyrimidine derivatives with expected cyclin-dependent kinase 2 inhibitory effect', EKB Journal Management System, 2(2), pp. 9-20. doi: 10.21608/aijpms.2022.77353.1075
Younes, A., Shawer, T., El-Sehrawi, H. Design, synthesis and antiproliferative evaluation of novel pyrazolo-pyrimidine derivatives with expected cyclin-dependent kinase 2 inhibitory effect. EKB Journal Management System, 2022; 2(2): 9-20. doi: 10.21608/aijpms.2022.77353.1075

Design, synthesis and antiproliferative evaluation of novel pyrazolo-pyrimidine derivatives with expected cyclin-dependent kinase 2 inhibitory effect

Azhar International Journal of Pharmaceutical and Medical Sciences
Article 2, Volume 2, Issue 2, June 2022, Page 9-20  XML PDF (1.01 MB)
Document Type: Original research articles
DOI: 10.21608/aijpms.2022.77353.1075
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Authors
Amal S Younes; Taghreed Z Shawer email ; Hend MA El-Sehrawi
Pharmaceutical Medicinal Chemistry and Drug Design Department, Faculty of pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
Abstract
A series of novel pyrazolopyrimidines 2-11 have been designed and synthesized. Depending on the screening A series of novel pyrazolopyrimidines 2-11 have been designed and synthesized. Depending on the screening program of NCI, 2-11 have been estimated in vitro for their anti-proliferative properties on 60 cell line subpanels. Among them, compounds 6 and 11 displayed excellent antiproliferative effects against glioma cell line (SF-539) with GI values of 85.85% and 63.65%, respectively. Therefore, the IC50 values for compounds 6 and 11 against the SF-539 cell line were obtained with the best results, using Roscovitine as a positive control. Compound 6 showed the best inhibitory activity with IC50 value of 11.1 μM, representing 1.5-folds the potency of Roscovitine, while compound 11 exhibited 71% the inhibitory activity of the reference used. Enzymatic inhibition studies on compound 6 show that it has activity on cyclin-dependent kinase 2 (CDK2/cyclinA) with IC50 equal 0.76 μM, compared to Roscovitine (IC50 = 0.44 μM). Compound 6 was tested for toxicity against normal human lung cell line (WI-38), and it possessed no toxicity against it. Its IC50 value was found to be 66.20 μM. A docking investigation was done to disclose interactions of compounds 6 and 11 in the CDK2 kinase's active site. Computational ADME analysis was achieved to ensure that, compounds 6 and 11 have appropriate pharmacokinetic and drug-likeness characteristics.
Keywords
4-d]pyrimidine; pyrazolo[3; 4-b]pyridine; CDK2 inhibitors
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