Synthesis, In Silico and Structural Insight of Flavonol Derivative Compounds as New Competitive Dengue NS2B/NS3 Protease Inhibitor

Dengue virus (DENV) is a single-stranded RNA virus that belongs to the Flaviviridae family and the genus lavivirus. Dengue virus infection can cause Dengue Hemorrhagic Fever (DD), it can lead to Dengue Hemorrhagic Fever (DHF). The main purpose of this study is to synthesis compound 2'-methoxy flavonol (2F) and its derivative (TF2) and also to predict the binding orientation of these molecules as inhibitor for dengue virus DENV-2 NS2B/NS3 serine protease. Synthesis was performed using stirring method, it was begun with compound 2'-hydroxy- 2-methoxychalcone and hydrogen peroxide as starting material. 2'-methoxy flavonol (2F) was obtained in the form of a white powder with a yield of 71.85%. Furthermore, compound 2F with 1-bromo-3-chloropropane reacted using reflux method, in order to obtain compound TF2 in form of white crystals with yield of 82.32%. The molecular structure of synthesized compounds was confirmed using spectroscopic analysis i. e. UV, FT-IR, 1H-NMR and 13C-NMR. Based on the molecular docking and density functional theory (DFT), it was shown that compound TF2 might be used as potential dengue DEN2 NS2B/NS3 serine protease inhibitor. This strategy is an early stage for discover new drugs for then it can be used as dengue virus inhibitors.