Malaysian Journal of Analytical Sciences, Vol 27 No 5 (2023): 1003 - 1016

 

BENZIMIDAZOLE DERIVATIVES AS POTENTIAL NEURAMINIDASE INHIBITORS: CONVENTIONAL AND MICROWAVE SYNTHESIS, In Vitro AND MOLECULAR DOCKING ANALYSIS

 

(Terbitan Benzimidazola yang Berpotensi sebagai Perencat Neuraminidase: Sintesis secara Konvensional dan Gelombang Mikro, Analisis In Vitro dan Pengedokan Molekul)

 

Nurasyikin Hamzah1, Shafida Abd Hamid1,4*, Aisyah Saad Abdul Rahim2, and Habibah Abdul Wahab3

 

1Department of Chemistry, Kulliyyah of Science, International Islamic University Malaysia, Bandar Indera Mahkota, 25200 Kuantan, Pahang, Malaysia

2Faculty of Pharmacy, UiTM Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia

3School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia

4SYNTOF, Kulliyyah of Science, International Islamic University Malaysia, Bandar Indera Mahkota, 25200 Kuantan, Pahang, Malaysia

 

*Corresponding author: shafida@iium.edu.my

 

 

Received: 27 March 2023; Accepted: 23 July 2023; Published:  30 October 2023

 

 

Abstract

As a continuous effort to discover potential neuraminidase (NA) inhibitors, two series of benzimidazole derivatives consisting of esters, 5(a–g) and carboxylic acid moieties, 6(a–g) were synthesised under conventional and microwave conditions. The efficiency of both methods was compared, and their ability to inhibit the action of NA enzyme was examined in silico and in vitro. The microwave synthesis of the target compounds was more efficient and convenient than the conventional method as the former accelerated the reaction from hours to minutes, giving comparable yields. All compounds obtained were confirmed by the 1H, 13C NMR, and mass spectroscopic data. Out of six compounds tested in the carboxylic acid series, only 6f showed inhibitory action towards NA with 15.2%. The binding interactions of 6(a–g) were investigated further by molecular docking on the NA active site (PDB ID: 3TI6). 6f was found to interact in the 430-loop cavity mainly by hydrophobic interactions. 6f interacted at different active sites compared to DANA and oseltamivir. Although the compounds showed low inhibitory action, with strategic structural improvements, the benzimidazoles have the potential to be developed as NA inhibitors.

 

Keywords: benzimidazole, MAOS, Neuraminidase inhibitor, Molecular docking, MUNANA

 

Abstrak

Sebagai usaha berterusan untuk menemukan perencat neuraminidase (NA) yang berpotensi, dua siri terbitan benzimidazola yang terdiri daripada ester, 5(a–g) dan moieti asid karboksilik, 6(a–g) telah disintesis dalam keadaan konvensional dan gelombang mikro. Kecekapan kedua-dua kaedah telah dibandingkan dan keupayaan mereka untuk merencat enzim NA telah diselidik secara in silico dan in vitro. Sintesis sebatian sasaran melalui gelombang mikro adalah lebih cekap dan mudah berbanding kaedah konvensional kerana proses tindak balas dipercepat dari beberapa jam ke minit, memberikan hasil yang setanding. Semua sebatian yang diperoleh adalah bertepatan dengan data 1H, 13C NMR, dan spektroskopi jisim. Daripada enam sebatian yang diuji dalam siri asid karboksilik, hanya 6f menunjukkan tindakan perencatan terhadap NA sebanyak 15.2%. Interaksi pengikatan 6(a–g) telah dikaji dengan lebih lanjut melalui pengedokan molekul terhadap tapak aktif NA (PDB ID: 3TI6). 6f didapati berinteraksi dalam rongga 430 gelung terutamanya oleh interaksi hidrofobik. 6f berinteraksi di tapak aktif yang berbeza berbanding DANA dan oseltamivir. Walaupun sebatian menunjukkan tindakan perencatan yang rendah, dengan penambahbaikan struktur strategik, benzimidazola mempunyai potensi untuk dibangunkan sebagai perencat NA.

 

Kata kunci: Benzimidazola, MAOS, Perencat neuraminidase, Pengedokan molekul, MUNANA

 

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