Next Article in Journal
Synthesis and Antibacterial Evaluation of Novel 1,3,4-Oxadiazole Derivatives Containing Sulfonate/Carboxylate Moiety
Previous Article in Journal
Serjanic Acid Improves Immunometabolic Markers in a Diet-Induced Obesity Mouse Model

This is an early access version, the complete PDF, HTML, and XML versions will be available soon.

Open AccessArticle

Synthesis and Biological Evaluation of Novel (thio)semicarbazone-Based Benzimidazoles as Antiviral Agents against Human Respiratory Viruses

1
Dipartimento di Farmacia, Università di Genova, Viale Benedetto XV 3, 16132 Genova, Italy
2
Rega Institute for Medical Research, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium
*
Author to whom correspondence should be addressed.
Molecules 2020, 25(7), 1487; https://doi.org/10.3390/molecules25071487 (registering DOI)
Received: 17 February 2020 / Revised: 16 March 2020 / Accepted: 23 March 2020 / Published: 25 March 2020
(This article belongs to the Section Medicinal Chemistry)
Respiratory RNA viruses are responsible for recurrent acute respiratory illnesses that still represent a major medical need. Previously we developed a large variety of benzimidazole derivatives able to inhibit these viruses. Herein, two series of (thio)semicarbazone- and hydrazone-based benzimidazoles have been explored, by derivatizing 5-acetyl benzimidazoles previously reported by us, thereby evaluating the influence of the modification on the antiviral activity. Compounds 6, 8, 16 and 17, bearing the 5-(thio)semicarbazone and 5-hydrazone functionalities in combination with the 2-benzyl ring on the benzimidazole core structure, acted as dual inhibitors of influenza A virus and human coronavirus. For respiratory syncytial virus (RSV), activity is limited to the 5-thiosemicarbazone (25) and 5-hydrazone (22) compounds carrying the 2-[(benzotriazol-1/2-yl)methyl]benzimidazole scaffold. These molecules proved to be the most effective antiviral agents, able to reach the potency profile of the licensed drug ribavirin. The molecular docking analysis explained the SAR of these compounds around their binding mode to the target RSV F protein, revealing the key contacts for further assessment. The herein-investigated benzimidazole-based derivatives may represent valuable hit compounds, deserving subsequent structural improvements towards more efficient antiviral agents for the treatment of pathologies caused by these human respiratory viruses.
Keywords: (thio)semicarbazone-based benzimidazoles; hydrazone-based benzimidazoles; anti-RSV activity; anti-influenza activity; anti-coronavirus activity; molecular modelling studies (thio)semicarbazone-based benzimidazoles; hydrazone-based benzimidazoles; anti-RSV activity; anti-influenza activity; anti-coronavirus activity; molecular modelling studies
Show Figures

Graphical abstract

MDPI and ACS Style

Francesconi, V.; Cichero, E.; Schenone, S.; Naesens, L.; Tonelli, M. Synthesis and Biological Evaluation of Novel (thio)semicarbazone-Based Benzimidazoles as Antiviral Agents against Human Respiratory Viruses. Molecules 2020, 25, 1487.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop