THE POTENTIAL ANTIMALARIAL DRUG OF ARYL AMINO ALCOHOL DERIVATIVES FROM EUGENOL: SYNTHESIS, in-vitro AND in-silico ANALYSIS OF BIOACTIVITY

• Published in: Rasāyan journal of chemistry 2023-07, Vol.16 (3), p.1425-1434
• Main Authors: Julianto, T. S., Rachmawaty, F. J., Tamhid, H. A., Putri, B. S.
• Format: Article
• Language: English
• ISSN: 0974-1496; 0974-1496
• DOI: 10.31788/RJC.2023.1636940

Malaria is a significant cause of death in numerous countries, and the discovery of effective drugs is crucial. In this research, a new method was employed to synthesize a derivative of aryl amino alcohol using eugenol. Initially, an epoxide compound called 2-methoxy-4-(oxiran-2-ylmethyl) phenol was synthesized from eugenol by reacting it with peroxyacetic acid in dichloromethane. Subsequently, the epoxide compound was subjected to a reaction with various amine compounds, including aniline, naphthylamine, and diphenylamine for 10 minutes under 100 W microwave conditions, resulting in the production of three derivative compounds of aryl amino alcohol. The antimalarial activity of these synthesized compounds was assessed in-vitro through an assay called heme polymerization inhibition activity (HPIA). Additionally, an in-silico analysis was conducted to evaluate the bioactivity of the three aryl amino alcohol derivatives by performing molecular docking with the Plasmepsin II enzyme. The identification of the products were determined using Fourier Transform Infrared (FTIR) spectrophotometry, proton nuclear magnetic resonance (1HNMR) spectrometry, and Electrospray ionization-Mass Spectrometry (ESI-MS). The research successfully obtained three aryl amino alcohol derivatives: 2-hydroxy-3-(phenylamino) propyl)-2-methoxyphenol, 4-(2-hydroxy-3- (naphthalene-1-ylamino) propyl)-2-methoxyphenol, and 4-(2-hydroxy-3-(diphenylamine)-2-methoxy phenol. All the synthesized compounds demonstrated lower IC50 values compared to chloroquine, indicating their potential as antimalarial drugs. Molecular docking studies revealed that these aryl amino alcohol derivatives effectively inhibited the activity of the Plasmepsin II enzyme