Synthesis and anticancer activity of some pyrido[2,3-d]pyrimidine derivatives as apoptosis inducers and cyclin-dependent kinase inhibitors

Author:

Abbas Safinaz E-S1,George Riham F1,Samir Eman M2,Aref Mostafa MA23,Abdel-Aziz Hatem A4

Affiliation:

1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt

2. Organic Chemistry Department, National Organization for Drug Control & Research, Cairo, Egypt

3. Medicinal Chemistry Department, Heliopolis University, Cairo 11777, Egypt

4. Department of Applied Organic Chemistry, National Research Center, PO Box 12622, Dokki, Giza, Egypt

Abstract

Aim: Due to emergence of resistance to available anticancer agents, there is a need to search for new cytotoxic agents. Methods: Pyrido[2,3- d]pyrimidines (4–6) and their tricyclic derivatives (7–13) were prepared and screened for their cytotoxicity against breast MCF-7, prostate PC-3 and lung A-549 cancer cell lines as well as normal fibroblasts WI-38. Results: The most active compounds were 6b, 6e and 8d compared with doxorubicin. Moreover, compounds 6b and 8d induced apoptosis in PC-3 and MCF-7, respectively via activation of CASP3 (in PC-3 only), Bax, p53 and down regulation of Bcl2 in addition to CDK4/6 inhibition. Conclusion: Pyrido[2,3- d]pyrimidine represents an important core for discovery of new potent cytotoxic agents acting on the cell cycle via apoptosis induction through either intrinsic or extrinsic pathways.

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

Reference19 articles.

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