Malaysian Journal of Analytical Sciences Vol 26 No 1 (2022): 47 - 57

 

 

 

 

SYNTHESIS, CHARACTERIZATION, AND IN-SILICO STUDIES OF CINNAMIC ACID DERIVATIVES TOWARDS DENGUE VIRUS

 

(Sintesis, Pencirian dan Kajian In-Siliko Sebatian Terbitan Asid Sinamik Terhadap Virus Denggi)

 

Anis Najwa Mohd Wahid¹, Nadia Mohamed Yusoff¹, Asnuzilawati Asari^1,2*, Siti Nor Khadijah Addis¹, Hanis Mohd Yusoff^1,2, Habsah Mohamad³, Fauziah Abdullah⁴

 

¹Faculty of Science and Marine Environment

²Advanced Nano Materials (ANoMa) Research Group, Faculty of Science and Marine Environment

³Institute of Marine Biotechnology

Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu, Malaysia

⁴Phytochemistry Programme, Natural Products Division,

Forest Research Institute of Malaysia, 52109 Kepong, Selangor, Malaysia

 

*Corresponding author: asnu@umt.edu.my

 

 

Received: 7 August 2021; Accepted: 18 December 2021; Published: 25 February 2022

 

 

Abstract

The dengue virus (DENV) has posed a serious global threat to human health for the past few decades. However, there are still no clinically approved antiviral drug available for the treatment of DENV. Cinnamic acid and its derivatives have attracted great attention due to their broad range of pharmacological properties. The present study aimed to synthesize and investigate the affinity of cinnamic acid derivatives against DENV. Six cinnamic acid derivatives (AC1-AC6) were synthesized by the reaction of substituted cinnamoyl chloride with the corresponding alcohol and amine. The structures of the compounds were confirmed by using ¹H and ¹³C Nuclear Magnetic Resonance (NMR) and mass spectrometry. The synthesized compounds were then simulated for molecular docking to investigate their binding affinity to the protein target of DENV-2 NS2B/NS3 protease. The in-silico study reveals that the compound AC5 has the highest binding affinity and fit into the allosteric pocket of DENV-2 NS2B/NS3 serine protease with van der Waals interaction, C-H bonding and a few pi interactions such as π-cation, π-lone pair, π-π T-shaped as well as π-alkyl interaction.

 

Keywords: cinnamic acid, synthesis, anti-dengue virus, docking

 

Abstrak

Virus denggi (DENV) memberikan ancaman sejagat yang serius dalam kesihatan manusia sejak beberapa dekad yang lalu. Walau bagaimanapun, masih belum ada ubat anti-virus yang diluluskan secara klinikal bagi rawatan DENV. Asid sinamik dan terbitannya telah menarik banyak perhatian oleh kerana sifat farmakologi yang mempunyai julat yang luas. Kajian ini bertujuan untuk mensintesis dan menyiasat afiniti terbitan asid sinamik terhadap DENV. Enam terbitan asid sinamik (AC1-AC6) telah disintesis dengan tindakbalas penukargantian sinnamoil klorida dengan alkohol dan amina. Struktur sebatian telah disahkan dengan menggunakan ¹H dan ¹³C Resonans Magnet Nukleus (NMR) dan spektrometer jisim. Sebatian yang telah disintesis kemudian disimulasikan dengan mengedok molekul untuk mengkaji sifat afiniti dengan protein sasaran iaitu protease DENV-2 NS2B / NS3. Kajian in-siliko mendedahkan bahawa sebatian AC5 mempunyai afiniti pengikatan tertinggi dan dapat memasuki poket alosterik DENV-2 NS2B / NS3 protease serin dengan interaksi van der Waals, ikatan C-H dan beberapa interaksi pi seperti π-cation, π -lone pair, π-π berbentuk T dan juga interaksi π-alkil.

 

Kata kunci: asid sinamik, sintesis, anti-virus denggi, mengedok

 

 

Graphical Abstract

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