DESAIN INHIBITOR GANDA 5-LOX/COX: SKRINING DAN OPTIMASI SENYAWA-SENYAWA DENGAN SUB-STRUKTUR 2-BENZILIDEN SIKLOHEKSANA-1,3-DION MENGGUNAKAN PEMODELAN FARMAKOFOR, DOCKING, DAN QSAR

Cyclooxygenase (COX) and 5-Lipoxygenase (5-LOX) are the main enzymes involved in inflammation process. Most of the anti-inflammation drugs only work by inhibiting COX activity. Considering that facts many researchs have been done to find new compounds as dual 5-LOX/COX inhibitor in order to find safer and more potent anti-inflammation drugs. One of the most interesting compounds to do further investigation as dual 5-LOX/COX inhibitor is 2-benzilliden cyclohexane-1,3-dione derivate. This research aimed to find lead compounds from many compounds that have 2-benzilliden cyclohexane-1,3-dione as sub-structure and optimize them using pharmacophore, docking and QSAR approach. Test compounds was obtained from PubChem database and then prepared and docked to 5-LOX protein which is produced by homology modeling and COX-2 protein wich have pdb code 3-NT1 with ligand-based and complex-based pharmacophore using MOE. QSAR analysis was used to improve accuracy of the scoring function by using docking score as the one of the QSAR descriptors. From the process of screening virtual done been gained 5 compounds with the value of pic50 prediction high ( more than 7 ) for enzymes 5-lox and cox, which is a compound with the code pubchem 10518783, 56640218, 22996969, 10682939, 68986386.The result of optimation did not found a compound that has the activity of an inhibitory 5-lox / cox larger than a compound of their parents.