Perpustakaan Digital ITB

Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. The current trend in research on anticancer drugs is to exploit particular traits or hallmarks unique to cancer cells. Among all the hallmark of cancer, the acquisition of unlimited replicative potential is a key step to ensure expansive tumour growth. Xanthone derivatives, such as 1-hydroxyl-3-aminoalkoxy xanthone derivatives have been proved having anticancer activity towards various cancer cells especially human gastric cancer (HGC) cell in which involved the activity of human topoisomerase II beta enzyme. The aim of the present research was to design xanthone derivatives as novel anticancer compounds based on Quantitative Structure Activity Relationship (QSAR) methods. Molecular structures were built using Gauss View 5.0.8 and optimized using Gaussian 09W software. The pharmacochemistry properties were calculated using MOE 2009.10 and multilinear statistical analysis was performed using SPSS Statistics 21.0. The validation was conducted by Leave One Out method. The designing of new derivatives were done by using Topliss scheme based on QSAR equation. The new derivatives were then docked into human topoisomerase II beta enzyme using AutoDock 4.2 software to predict their interactions. The best QSAR equation obtained was Log IC 50= 39.587+ (6.540 x Density) + (4.849 x AM1_HOMO) + (-0.603 x AM1_LUMO) + (-0.010 x LogS). There were 15 new compounds which were predicted having lower IC50 compared to the lead compound based on QSAR equation. Seven derivatives have better free binding energy, and one compound of 3-[3 (diethylamino) propoxy]-1-hydroxy-9H-xanthen-9-one shows the best affinity (the value of free binding energy was -5.03 kcal/mol ) to Human topoisomerase II-beta enzyme. Among all the compound, 3g(1) is the prospective novel xanthone derivatives for further study.