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

摘要: Respiratory RNA viruses are responsible for recurrent acute respiratory illnesses that still represent a major medical need. Previously we developed large variety of benzimidazole derivatives able to inhibit these viruses. Herein, two series (thio)semicarbazone- and hydrazone-based benzimidazoles have been explored, by derivatizing 5-acetyl previously reported us, thereby evaluating the influence modification on antiviral activity. Compounds 6, 8, 16 17, bearing 5-(thio)semicarbazone 5-hydrazone functionalities in combination with 2-benzyl ring core structure, acted as dual inhibitors influenza A virus human coronavirus. For syncytial (RSV), activity is limited 5-thiosemicarbazone (25) (22) compounds carrying 2-[(benzotriazol-1/2-yl)methyl]benzimidazole scaffold. These molecules proved be most effective agents, reach potency profile licensed drug ribavirin. The molecular docking analysis explained SAR around their binding mode target RSV F protein, revealing key contacts further assessment. herein-investigated benzimidazole-based may valuable hit compounds, deserving subsequent structural improvements towards more efficient agents treatment pathologies caused