IN SILICO STUDY OF FLAVONOID COMPOUND OF MACARANGA GIGANTEA LEAVES AS ANTIMALARIA USING PHARMACOLOGICAL NETWORK MODEL AND MOLECULAR DOCKING METHODS

• Main Author: Alrayan, Reza
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/74216
• Institution: Institut Teknologi Bandung

Malaria is an infectious disease caused by parasites of the genus Plasmodium. The disease has been a global problem because it is difficult to eliminate. In this regard, efforts to develop new antimalarial drugs resulting from exploration of native Indonesian natural materials through a rational and scientific approach are important. In previous studies, flavonoid compounds from Macaranga gigantea leaf extract were indicated to have antimalarial activity. This study began with screening data on test compounds, genes and target proteins for antimalarials from the flavonoids of Macaranga gigantea leaves through database and literature reviews. Prediction of Lipinski charateristic and pharmacokinetic profiles of test compounds using BIOSig then followed. A pharmacological network model (PNM) was later carried out to determine the linkage of the test compound with the target gene as an antimalarial. The test compound and identified target protein were reconstructed into a threedimensional model for molecular docking studies using AutoDock Tools Ver 1.5.7 to study the inhibitory ability of the test compound protein. The visualization of the binding sites of the test compounds, the types of bonds and the protein amino acids involved in malaria elimination were confirmed with the BIOVIA DSV program. Five active compounds of Macaranga gigantea flavonoids have been identified, namely apigenin, glyasperin A, macagigantin, brossuflavonol F and schweintifurtin C. Through literature studies and PNM, four target proteins were obtained for molecular docking. The pharmacokinetic profile shows that the tested compound has the criteria for a drug that is feasible to be administered orally but cannot penetrate the blood brain barrier. The results further indicated the genes thought to be involved in the antimalarial activity of the M. gigantea flavonoids, which include ABCB1, ABCG2, PTGS2, HSP90AA1, ACE, CYP3A4, AHR, CYP2C19, IL2 and CXCR4. glyasperin A has the best binding affinity and inhibition of the target Mitochondrial bc1 of the genus Plasmodium falciparum with a binding energy of -11.41 Kcal/mol and an inhibition constanta of 0.004 µmol. apigenin was consistently shown to bind to all tested proteins. Amino acids of the test compounds which bind to the co-crystailized ligand and the comparator drug were expected to produce antimalarial activity. Overall, this in silico study demonstrated the antimalarial potential of Macaranga gigantea leaf flavonoids.