CURCUMIN DERIVATIVES POTENTIAL AS INHIBITOR OF NON-RECEPTOR TYROSINE KINASE SYK

• Main Author: Amirah Nur Rahmi, Hanan
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/60610
• Institution: Institut Teknologi Bandung

Cancer is the world’s second highest cause of death. One of the causes of cancer is an abnormal genome, which the damage of the genes that regulate cell growth, proliferation, and differentiation. Currently, there are many types of cancer treatment, including chemotherapy, radiotherapy, and surgery. However, various types of treatment are still considered to cause dangerous side effects. Therefore, anticancer drugs have been developed from whether synthetic or natural compounds. The drugs are expected to work specifically to stop or at least inhibit the growth of cancer cells and produce minimal and harmless side effects. One of the key-enzymes in the signaling pathway and plays a role in regulating cellular responses such as cell proliferation and differentiation is Spleen Tyrosine Kinase (SYK). The works made by researchers to inhibit the growth and cancer cells development is to find compounds that can act as an inhibitor to SYK enzyme. Currently, there is only one commercial inhibitor of SYK, fostamatinib. Therefore, it is necessary to explore other compounds that have potential to be SYK inhibitors. One of the potential sources is natural compounds and synthetic products. One of the natural compounds that reported to have various bioactivity is the derivatives of curcumin compounds. Curcumin is an active polyphenolic compound found in the turmeric plant from the Zingiberaceae family. Many studies have shown that curcumin has various biological activities such as anti-inflammatory, antioxidant, antibacterial, and anticancer. Therefore, in this study, curcumin and its 30 derivative compounds were selected to determine the most potential compounds to become SYK inhibitors. The selection of inhibitors is done by molecular docking method using Autodock Vina program. There are two important components in the docking simulation. There are searching algorithm that are used to find various optimal ligand configurations at the receptor site and scoring functions that are used to develop docking results based on their binding affinity. The PDB code of SYK protein used in this study is 4XG3. Fostamatinib was used as the standard inhibitor in this study. From 31 candidate of inhibitor compounds, docking scores ranged from -6.3 kcal/mol to -8.8 kcal/mol. Based on the results of the study, it is known that the most potential derivative of curcumin to be an inhibitor of SYK is (1E,6E) -1,7- bis(4-hydroxy-3-methoxyphenyl)-4-(phenylmethyldene) hepta-1,6-diene -3.5-diones (51). Compound (51) has good activity against SYK in terms of the docking score and its interaction with important residues on the SYK binding site. The important residues that become the key to the interaction of SYK inhibition are Met488 as gatekeeper residue and Asp512 as catalytic residue.