HUBUNGAN KUANTITATIF STRUKTUR-AKTIVITAS (HKSA) TURUNAN 4-TIAZOL-N-(PIRIDIN-2-IL) PIRIMIDIN-2-AMINA SEBAGAI INHIBITOR ENZIM CYCLIN-DEPENDENT KINASE 6 (CDK6)

• Main Author: Seanjaya, Jessica
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/40122
• Institution: Institut Teknologi Bandung

Breast cancer is the second cancer that causes the most deaths and affects women. One factor of the breast cancer is excessive expression of CDK6 enzyme which is a cell cycle regulating enzyme during the transition of G1 to S phase. The derivatives of 4-thiazol-N-(pyridin-2-yl)pyrimidin-2-amine have CDK6 enzyme inhibitory activity which could be developed as a breast cancer compounds. The objective of the present research is determining the best quantitative structure activity relationship (QSAR) equation of 4-thiazol-N-(pyridin-2-yl)pyrimidin-2-amine derivatives and designing new derivatives that have lower IC50value and more optimal binding with the CDK6 receptor. As much as 37 compounds of training set were designed using GaussView 6.0.16 and were optimized using Gaussian 09W, the physicochemical parameters of each compound were then calculated by the calculation of 14 descriptors using MOE 2009.10. Statistical analysis give the best QSAR equation which was log IC50(µM) = 48,629 (±8,967) + 53,134 (±10,279) x density + 1,261 (±0,608) x mr 0,052 (±0,010) x ASA_H + 2,552.10 –5 (±2,254x 10 –6 ) x AM1_Eele + 0,132 (±0,036) x vol. Derivatives of parent compound (compound 83) were designed based on Craig plot; therefore 56 compounds that have lower IC50value than parent compound were obtained. The compounds were docked using Autodock 4.2.6 MGLTools 1.5.6rcl3 and visualized using BIOVIA Studio Visualizer 2017. Compound 2e5e, 2e5v, 5e14v, dan 5r14v are predicted to have lower IC50value than that of the parent compound, could form stable complexes, and have good affinity to the CDK6 receptor so could be further study as anti-breast cancer.