• SAAMANTHI M
• Dr.S.ARUNA
• Dr.R.GIRIJA
• S.GUNASEKAR

ABSTRACT: The wide occurrence of the heterocyclic molecules in bioactive natural products and pharmaceuticals has made them as important synthetic targets. The chemistry of pyrimidines has become increasingly important as a result of recent developments in medicinal chemistry. Two moles of substituted aldehyde and substituted ketones were stirring 12 hrs. Then the mixture was cooled and filtered. Recrystallised with ethanol producing substituted chalcone (2a-k). The chalcones are treated with urea refluxed at 80oC in a heating mantle for 6 hrs in the presence of 10% sodium hydroxide in ethanol produced trisubstituted pyrimidine derivatives (3a-k). Cyclin-dependent kinases (CDK) control the cell division cycle (CDC). The deregulation of CDK2 is closely related to many cancers. CDK2 is utilized as one of the most studied kinase targets in oncology. It plays an important role in regulating various events of eukaryotic cell division cycle. Accumulated evidences indicated that over expression of CDK2 should cause the abnormal regulation of cell-cycle, which would be directly associated with hyper proliferation in cancer cells. Therefore, CDK2 was regarded as a potentially therapeutic target for cancer therapy. It is possible to develop pharmacologically relevant cytotoxic agents by specifically inhibiting CDK2 activity with lesser toxicity than traditional chemotherapeutic agents. The insilico docking studies was performed Schrodinger Maestro 11.9. From the docking results, The heterocycle of 4-(4-Chlorostyryl)-6-(4-Chlorophenyl)pyrimidin-2-(1H)-one, (AS010) shown interaction with THR-14,LYS-33,LEU-83,ASN-132,LYS-129. However, it was noted that there is a hydrogen bond between the derivatives of Pyrido(4,3-d)Pyrimidine and AS010 was potent inhibitor for CDK2.

Keywords: Pyrido[4,3-d]pyrimidine, Cyclin dependent kinase ,Anti-cancer activity, AS010, Schrodinger Maestro 11.9, Molecular docking.

"ANTICANCER EVALUATION, AND MOLECULAR DOCKING STUDIES OF SOME NOVEL SUBSTITUTED PYRIDO[4,3-D]PYRIMIDINES AS CYCLIN-DEPENDENTKINASE 2 (CDK2) INHIBITORS", International Journal of Emerging Technologies and Innovative Research (www.jetir.org), ISSN:2349-5162, Vol.6, Issue 6, page no.440-451, June 2019, Available :http://www.jetir.org/papers/JETIR1906V62.pdf

"ANTICANCER EVALUATION, AND MOLECULAR DOCKING STUDIES OF SOME NOVEL SUBSTITUTED PYRIDO[4,3-D]PYRIMIDINES AS CYCLIN-DEPENDENTKINASE 2 (CDK2) INHIBITORS", International Journal of Emerging Technologies and Innovative Research (www.jetir.org | UGC and issn Approved), ISSN:2349-5162, Vol.6, Issue 6, page no. pp440-451, June 2019, Available at : http://www.jetir.org/papers/JETIR1906V62.pdf