STUDI HUBUNGAN KUANTITATIF STRUKTUR-AKTIVITAS (HKSA) SENYAWA TURUNAN 1,2,4- TRIAZOL SEBAGAI KANDIDAT ANTIKANKER KOLON

• Main Author: Tansil, Welly
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/48739
• Institution: Institut Teknologi Bandung

Colon cancer is the second leading cause of deaths at all ages in the world. One of the target from using chemotherapeutic drugs is the vascular endothelial growth factor (VEGF). VEGF has a important role in endothelial cell proliferative and migration process. One journal states that triazol ring has potential to be colorectal anticancer with VEGF as the protein target. The aim of this research is determining the best model of quantitative structure activity relationship (QSAR) equation from 1,2,4-triazole derivatives and also designing new compounds that have higher activity. 14 types of descriptor were used to generate QSAR equation has represented electronic, steric and lipophilic parameter of Hansch equation. The value of descriptor in each compounds were calculated by using Gaussian09 and MOE 2014.0901 programs. Statistical results and QSAR equation were determined by IBM SPSS 25 program. New compounds was designed by considering QSAR equation and expected to have higher activity than lead compound. Interactions were studied using docking simulation with AutoDock 4.2.6 and MGLTools 1.5.6 programs. Then, the results were visualized using BIOVIA Studio Visualizer 2019 and VMD 1.9.4. Based on the result, best QSAR equation is log (1/IC50) = 1,79387 ?0,07518 x (dipole moment) ?0,00064 x (Eelectronic) 7,40549 x (HOMO) + 13,8630 x (LUMO) + 0,07224 x (log S) + 0,05682 x (Evdw)?0,00773 x (volume). There were 3 new compounds (A, B, and C) which were predicted having higher activity. 2 of them (A and C) showed better affinity and interaction with VEGFR2 protein than lead compound. Hence, compound A and C are the prospective novel 1,2,4-triazole derivatives for further study.