N-alkylation of amines for the synthesis of potential antiviral agents: A structural modification approach
Nadia Arrousse,
Elyor Berdimurodov,
Mariia Bogacheva,
Fathiah Zakham,
Soukaina Esslali,
Sghir EL Kadiri,
Mustapha Taleb,
Olli Vapalahti
Affiliations
Nadia Arrousse
School of Science and Engineering, Al Akhawayn University in Ifrane, Hassan II avenue, 53000 Ifrane, Morocco; Laboratory of Engineering, Electrochemistry, Modelling and Environment (LIEME), Faculty of Sciences, University Sidi Mohamed Ben Abdellah, Fez, Morocco; Corresponding author. School of Science and Engineering, Al Akhawayn University in Ifrane, Hassan II avenue, 53000 Ifrane, Morocco
Elyor Berdimurodov
Faculty of Chemistry, National University of Uzbekistan, Tashkent, 100034, Uzbekistan; Physics and Chemistry, Western Caspian University, AZ-1001, Baku, Azerbaijan; University of Tashkent for Applied Sciences, Str. Gavhar 1, 100149, Tashkent, Uzbekistan; Corresponding author. Faculty of Chemistry, National University of Uzbekistan, Tashkent, 100034, Uzbekistan.
Mariia Bogacheva
Viral Zone Research Unit, Faculty of Medicine, University of Helsinki, Finland
Fathiah Zakham
Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland; Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland; Corresponding author. Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Soukaina Esslali
Laboratory of Chemistry-Biology Applied to the Environment, Chemistry Department, Faculty of Sciences, Moulay-Ismail University, B.P. 11201, Zitoune, Meknes, Morocco
Sghir EL Kadiri
Laboratory of Applied Chemistry & Environment (LCAE), Faculty of Science, Mohammed First University, Oujda, Morocco; Corresponding author.
Mustapha Taleb
Laboratory of Engineering, Electrochemistry, Modelling and Environment (LIEME), Faculty of Sciences, University Sidi Mohamed Ben Abdellah, Fez, Morocco
Olli Vapalahti
Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland; Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland
The threat of emerging viral outbreaks has increased the need for fast and effective development of therapeutics against emerging pathogens. One approach is to modify the structure of existing therapeutic agents to achieve the desired antiviral properties. Here, we attempted to synthesize a new antiviral compound by modifying the structure of chloroquine using the N-alkylation of the primary amine (N1,N1-diethylpentane-1,4-diamine) that is used in chloroquine synthesis. Chloroquine is commonly used to treat malaria. Like chloroquine, chloroquine is used for treating conditions such as rheumatoid arthritis, lupus, and malaria. For instance, in malaria treatment, it targets and inhibits the growth of the malaria parasite, aiding in its elimination from the body. The synthesized compounds MP1, C1, and TT1 were further tested in vitro against the B.1 lineage of SARS-CoV-2. One of the compounds, MP1, demonstrated minor effectiveness, with an IC50 of XX at only a high concentration (at a concentration of 60 μM) and decreased both the number of SARS-CoV-2 copies and the amount of infectious virus. Although the synthesized compounds failed to markedly inhibit SARS-CoV-2, this could be a pontial mechanism for manipulating the drug structure against other pathogens. MP1, TT1, C1, and chloroquine diphosphate were used as ligands for molecular docking to determine the principal interactions between these compounds and the active site of the protein downloaded from the Protein Data Bank (PDB ID: 6lzg). Finally, ADMET assays were performed on the synthesized compounds to determine their pharmacokinetics and bioavailability.
