Benzimidazole derivatives as potential neuraminidase inhibitors: conventional and microwave synthesis, in vitro and molecular docking analysis

• Main Authors: Hamzah, Nurasyikin, Abd Hamid, Shafida, Abdul Rahim, Aisyah Saad, Abdul Wahab, Habibah
• Format: Article
• Language: English; English
• Published: Malaysian Analytical Sciences Society (ANALIS) 2023
• Subjects: QD Chemistry; RM300 Drugs and their action
• Online Access: http://irep.iium.edu.my/107762/7/107762_Benzimidazole%20derivatives%20as%20potential%20neuraminidase%20inhibitors.pdf; http://irep.iium.edu.my/107762/13/107762_Benzimidazole%20derivatives%20as%20potential%20neuraminidase%20inhibitors%20conventional%20and%20microwave%20synthesis_Scopus.pdf; http://irep.iium.edu.my/107762/; https://mjas.analis.com.my/mjas/v27_n5/pdf/Hamzah_27_5_8.pdf
• Institution: Universiti Islam Antarabangsa Malaysia

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