SENYAWA ANTI-AGING PALMITOIL PEPTIDA: PENGUJIAN TOKSISITAS AKUT PADA EMBRIO ZEBRAFISH (DANIO RERIO), STUDI INTERAKSI TERHADAP RESEPTOR, DAN PREDIKSI TOKSISITAS SECARA IN SILICO

• Main Author: Natalia, Stella
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/66094
• Institution: Institut Teknologi Bandung

Skin aging is a degenerative process that affects its structure as a result of intrinsic factors and extrinsic factors, such as exposure to ultraviolet radiation. Indonesia is a tropical country where the citizens are prone to skin aging caused by the sun's ultraviolet radiation. Many anti-aging compounds have been used to treat and prevent skin aging, some of which are palmitoyl oligopeptide (PO), palmitoyl tetrapeptide-7, acetyl hexapeptide-8, palmitoyl pentapeptide-4, palmitoyl tripeptide-8 (PT8), and palmitoyl tripeptide-5 (PT5). Therefore, this study aimed to determine the interaction of these peptides on receptors in Homo sapiens and predict their toxicity in silico, and also determined the safety level of palmitoyl tripeptide-5 and palmitoyl tripeptide-8 using the acute toxicity test on zebrafish embryos. The target proteins used were matrix metalloproteinase-1 or MMP-1 (PDB ID: 966C), matrix metalloproteinase-9 or MMP-9 (PDB ID: 5UE4), human fibroblast stromelysin-1 or MMP-3 (PDB ID: 1CIZ), and neutrophil elastase or NE (PDB ID): 3Q77). The three-dimensional structure of test compounds were obtained from molview.org, then optimized through GaussView 6.0 and Gaussian 09W. The molecular docking method was validated using the AutoDock 4.2.3 program. The results were analyzed using Biovia Discovery Studio 21.1.0 and toxicity was predicted using Toxtree 3.1.0.1851 and Vega 1.1.5. Palmitoyl tripeptide-5 was predicted to have the best interaction with all target proteins, indicated by ?G = - 3,27 kcal/mol (MMP-1), -6,53 kcal/mol (MMP-3), -3,89 kcal/mol (MMP-9), and -4,93 kcal/mol (NE). The toxicity of all the tested compounds were predicted to be high based on the Cramer Rules, while based on the Kroes TTC, all the tested compounds were predicted to have no safety problems and cause skin sensitization. In addition, PO and PT8 were predicted to be carcinogenic based on Benigni Rulebase. Predictions of acute and chronic toxicity using VEGA 1.1.5 for PT5 and PT8 were high and moderate. The LC50 value of PT5 in the sample A sample was 33,544 mg/L, while the LC50 value of PT8 in the sample B sample was 2.936 mg/L. Therefore, based on the classification of acute toxicity from Ecotoxicity Categories for Terrestrial and Aquatic Organisms, PT5 was classified as slightly toxic, while PT8 was classified as toxic.