STUDI INTERAKSI SENYAWA ASAM KOJIC, AHA, BHA, PHA, VITAMIN A, VITAMIN C DALAM KOSMETIK SEBAGAI INHIBITOR TYROSINASE RELATED PROTEIN-1, CARBONIC ANHYDRASE 1 DAN MATRIKS METALLOPROTEINASE-1 SERTA PREDIKSI TOKSISITAS SECARA IN SILICO

• Main Author: Fadiyah, Refina
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/56655
• Institution: Institut Teknologi Bandung

Skin aging is a complex process that can be caused by ultraviolet light that causes changes in the skin layer and in the appearance of the skin. Skin aging is a common case in the developed age group, especially in Indonesia, which is a tropical country where the sun shines all year round. Applying cosmetics that contain compounds with anti-aging activity is one of the strategies to prevent and treat skin aging. This research aimed to discover a new anti-aging compound candidate by predicting the interaction of compounds commonly used in cosmetics as inhibitors of Tyrosinase Related Protein 1 (TYRP-1), Carbonic anhydrase 1 (CA-1), and Matrix metalloproteinase-1 (MMP-I) enzymes using molecular docking method as well as predicting their toxicity. The target proteins used in this study were TYRP-1 (PDB ID: 5M8M), CA-1 (PDB ID: 6F3B), and MMP-1 (PDB ID: 2TCL). The macromolecules were prepared using BIOVIA Discovery Studio v21.1.0 program and the docking parameters were validated using AutoDock 4.2.6 program. The three-dimentional structures of the compounds were made using Avogadro and optimized using ORCA program using Density Functional Theory (DFT) B3LYP with 6-31G method. Test compounds were docked to the target using the AutoDock 4.2.6 program. The docking result were analyzed by using BIOVIA Discovery Studio v21.1.0 program. The toxicity was predicted using Toxtree v3.1.0 and Vega 1.1.5 programs. Based on the free energy binding and the interaction with key amino acids, mandelic acid was predicted to have the most potential as a TYRP-1 inhibitor which interacted to 13 amino acids that is similar to the native ligand binding with free energy binding –2.94 kcal/mol. Retinol was predicted to have the most potential as a CA-1 inhibitor that interacted to 13 similar amino acids to the native ligand with free energy binding -6.44 kcal/mol. Retinol was predicted to have the best interaction against MMP-1, it could bind to the same amino acids as which native ligand interacted to with free energy binding -5.14 kcal/mol. Based on the Toxtree and Vega programs, retinol may cause skin sensitization. Retinol was predicted to be a Schiff base on skin sensitization parameters and mandelic acid was predicted to potentially cause development toxicity. Both compounds were predicted to be relatively non-toxic based on the parameters of skin irritation and corrosion, eyes irritation and corrosion, carcinogenicity, mutagenicity.