Synthesis of 3'-methoxy flavonol and its derivatives as potential inhibitors for Dengue NS2B/NS3 and molecular insight into binding interaction

Abstract

Background: Infection with the Dengue virus can result in dengue fever (DD), which can progress to dengue hemorrhagic fever (DHF). Objective: In this work, molecule 3'-methoxy flavonol (3F) and its derivatives (T3F) were synthesized because they may be used to develop dengue antiviral DENV-2 NS2B/NS3 serine proteases. Method: Compound 2'-hydroxy-3-methoxy chalcone and hydrogen peroxide are used in the stirrer method to synthesize compound 3F with a yield of 33.24%, and yellow crystals of the 3F compound were produced. Results: The substance T3F was produced as white crystals with a yield of 69.42% by reacting compound 3F with ethyl chloroacetate using the reflux technique. Compound 3F exhibited absorption at maximal wavelengths of 212 nm, 244 nm, and 344 nm according to UV-Vis spectroscopy. UV-Vis spectroscopy of compound T3F revealed absorption at maximal wavelengths of 212 nm, 243 nm, and 320 nm. While a C=O ester group was replaced in the T3F synthesis step, the FT-IR spectroscopy of the 3F molecule revealed the existence of an OH group. Conclusion: Based on docking results, compound T3F has a binding free energy value that is extremely similar to that of panduratin A. Thus, it revealed that the T3F molecule has the potential to be an inhibitor of the NS2B/NS3 Protease virus DENV-2.

Sintesis, Karakterisasi Struktur, dan Kajian In Silico Potensi 2'-Hidroksicalkon dan Flavonol Ter¬¬¬substitusi Trimetoksi sebagai Inhibitor Main Protease (MPro) SARS-CoV-2

“…Sinyal-sinyal yang muncul pada daerah karbon aromatik senyawa F 345 ini ditampilkan dengan lebih detail pada Gambar S1 15 (Lihat Supporting Information). Penandaan sinyal-sinyal karbon yang muncul pada spektrum 13 C NMR senyawa F 345 pada Gambar 7(b) tersebut telah dipastikan melalui perbandingan data pergeseran kimia karbon-karbon antara senyawa F 345 pada penelitian ini dengan senyawa 3F yang telah dilaporkan oleh peneliti sebelumnya (Frimayanti et al, 2023). Berdasarkan perbandingan yang telah dilakukan, sebagian besar data pergeseran kimia karbon-karbon pada senyawa F 345 (pergeseran kimia yang diwarnai biru) memiliki kemiripan dengan data pergeseran kimia karbonkarbon pada gugus kromen senyawa 3F, sebagaimana dapat dilihat pada Gambar SI 16 (Lihat Supporting Information).…”