HUBUNGAN KUANTITATIF STRUKTUR DAN AKTIVITAS SENYAWA TURUNAN (S)-5-CHLORO-N-((3-(4-(4- ((DIETHYLAMINO)METHYL)THIAZOL-2-YL)PHENYL)-OXOOXAZOLIDIN-5-YL)METHYL)THIOPHENE-2-CARBOXAMIDE SEBAGAI INHIBITOR FAKTOR XA

• Main Author: Suryadi, Aris
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/44650
• Institution: Institut Teknologi Bandung

Stroke remains a leading cause of death in Indonesia, even in the world. According to the Basic Health Research by Ministry of Health Republic of Indonesia the prevalence of stroke in Indonesia reached 8.3 per 1000 in 2007 and increased to 12.1 per 1000 in 2013. In the treatment of stroke, one of the drugs that can be used is a factor Xa inhibitor (blood clotting factor). This study aims to determine the equation of Quantitative Structure and Activity Relationship (QSAR), new derivatives with activity of factor Xa inhibition and affinity ligand-receptor higher than the parent compound (s)-5-chloro-N-((3-(4-(4-((diethylamino)methyl)thiazol-2-yl)phenyl)-2-oxooxazolidin-5- yl)methyl)thiophene-2-carboxamide. ChemDraw and Gaussian software was used for modeling and geometry optimization of the structure of the compound. Descriptor as parameters of the physicochemical properties of the compounds were then calculated using the Molecular Operating Environment (MOE 2009.10) software and statistically analyzed using the software of SPSS statistics 21.0. The equation of QSAR which was generated from the data analysis was then validated using the Leave One Out (LOO) method. The equation was used to predict activity (IC50) of the new compounds derived from the parent compound. The new derivatives which have a higher activity (lower IC50) were interacted (docking) to the receptor using Autodock Tools 4.5.6 software. The docking process generated amino acid residues, inhibition constants, binding energy, the number and length of hydrogen bonds that were used to assess the affinity of compounds to the receptor. The validation process of docking was done by redocking the native ligand to the receptor to get Root Mean Square (RMSD) < 2. QSAR equation for (s)-5-chloro-N-((3- (4-(4-((diethylamino)methyl)thiazol-2-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)thiophene-2- carboxamide derivatives as factor Xa inhibitor is log IC50 = ?3.738 + (?2.43E-06 x AM1_Eele) + (0.139 x logs) + (1.288 x mr) + (?0.034 x vol). The results showed that seven new compounds have lower IC50 and higher affinity than the parent compound. They are compounds of 1, 2, 3, 5, 7, 13, 14, and 15.