MOLECULAR DOCKING AND ANTIPROLIFERITIVE AS CYCLIN - DEPENDENT KINASE 2 INHIBITOR

• Main Author: Rizki Fadhil Pratama, Mohammad
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/78827
• Institution: Institut Teknologi Bandung

Cyclin-dependent kinase 2 (CDK2), a kinase enzyme involved in regulating transition from Gl phase to S phase on cell cycle of eukaryote organisms, is a potential target for cancer therapy by hold the cell cycle in Gl phase. Artemisinin, a group of anti-malarial compound and its derivatives are known to have cytotoxic activity associated with termination of proliferation in Gl phase of cancers cells caused by down-regulation of CDK2 The present study aims to determine the most potent activity of artemisinin derivatives as CDK2 inhibitor. Docking against CDK2 showed that artesunate provide most negative free binding energy and lowest inhibition constants - 11.7 kcal/mol and 2.66 nM, respectively. Blind docking artesunate against CDK2 showed a competitive inhibitor mechanism on ATP-binding catalytic site of CDK2 Artesunate show higher affinity towards ATP catalytic site compared to some competitive CDK2 inhibitors with amino acids at position 13 to 16 had important influences towards affinity of artesunate. As a confirmation test we conducted antiproliferative effect test using yeast model with Candida albicans as test subjects. The measured parameters were the number of colonies after exposured to artesunate based on yeast-plate count methods. The antiproliferative test results showed that artesunate inhibits the growth of yeast colonies within IC50 value 32.73 gM. This showed that artesunate has antiproliferative effects as CDK2 inhibitor and should be potential to be developed as cancer therapy.