Activity of bis(7-hydroxycoumarin) Mannich bases against bovine viral diarrhoea virus

• Published in: Antiviral research Vol. 134; pp. 153 - 160
• Main Authors: Ibrahim, Munjed M., Mazzei, Mauro, Delogu, Ilenia, Szabó, Róbert, Sanna, Giuseppina, Loddo, Roberta
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-10-2016
• Subjects: Animals; Antiviral agents; Antiviral Agents - pharmacology; Bovine viral diarrhea virus; BVDV; Cattle; Cell Line; Coumarin derivatives; Diarrhea - veterinary; Diarrhea - virology; Diarrhea Viruses, Bovine Viral - drug effects; Flaviviridae; Mannich bases; Mannich Bases - chemical synthesis; Mannich Bases - chemistry; Mannich Bases - pharmacology; Structure-Activity Relationship; Umbelliferones - chemical synthesis; Umbelliferones - chemistry; Umbelliferones - pharmacology; Antiviral agents; BVDV; Coumarin derivatives; Mannich bases; Flaviviridae
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2016.07.022

Some Mannich bases of 7-hydroxycoumarins (3–6) with piperazine or other amines bearing two secondary amine groups were prepared and tested against viruses representative of RNA families. All compounds were symmetrical and possessed two identical coumarin moieties with respect to one diamine. In the series of 7-hydroxy derivatives, 3a was endowed with a significant activity against BVDV. Then, some of these double Mannich bases were alkylated and acylated. Among the propyloxy derivatives, only 3f showed a modest activity against BVDV. Among the acyl derivatives, the p-nitrobenzoyl derivative 3i emerged as the most active compound; in this series, the p-nitrobenzoyl derivative 3j also exhibited good action against BVDV and modest activity against CVB-5. On the whole, the compounds presented here show some differences, with respect to previous studies in terms of SAR from similar Mannich bases of 7-hydroxycoumarin.
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•Mannich bases of 7-hydroxycoumarins are of great interest to medicinal chemistry.•We synthesized new Mannich bases of 7-hydroxycoumarins (3–6) with piperazine or other amines bearing two secondary amine groups.•We evaluated their antiviral activity against different RNA and DNA viruses.•The p-nitrobenzoyl derivative 3i showed most potent activity against Bovine Viral Diarrhoea Virus.