POTENTIAL CAFFEINE DERIVATIVE COMPOUNDS AGAINST ANTICANCER- RELATED TYROSINE KINASE AXL

• Main Author: Fasha, Adzkia
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/57302
• Institution: Institut Teknologi Bandung

Cancer is one of the leading causes of death in the world. One of the proteins that play a role in the process of cancer development is AXL. AXL is overexpressed in various cancer cells which causes AXL to become one of the main targets in cancer treatment. However, until now, drug selectivity against AXL is still a challenge that needs to be overcome. In this study, screening as an early stage of drug design was carried out using the molecular docking method against AXL with various compounds, those are 7-aminocephalosporanic acid (7-ACA), 6-aminopenyclic acid (6-APA), cyclo (L-Leu-D-Pro), (R) 4-ethoxy-2-hydroxy-4-oxobutanoat acid, and 14 derivative compounds of caffeine. The docking molecular was carried out using the Autodock Vina program with a genetic algorithm and the interaction analysis was carried out using the Ligplot+ program. AXL inhibitor candidates were identified by the lowest docking score and the presence of important amino acid residues involved. In this study, there are 8 derivative compounds of caffeine that had the best docking scores, ranging from -7.2 kcal/mol to -8.0 kcal/mol. The interaction between AXL and 8 derivative compounds of caffeine also involves important amino acid residues that act as a backbone, those are Met623 and Phe622 and a residue that plays an important catalytic role, that is Asp690. From these two things, 8 derivative compounds of caffeine are predicted to have a strong level of inhibition against AXL, so they can be considered as candidates for AXL inhibitors.