Anti-HIV activity of stilbene-related heterocyclic compounds

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 15; pp. 4075 - 4079
• Main Authors: Bedoya, Luis M., del Olmo, Esther, Sancho, Rocío, Barboza, Bianca, Beltrán, Manuela, García-Cadenas, Ana E., Sánchez-Palomino, Sonsoles, López-Pérez, José L., Muñoz, Eduardo, Feliciano, Arturo San, Alcamí, José
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.08.2006; Elsevier
• Subjects: Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Benzalphthalides; Biological and medical sciences; Gene Products, tat - antagonists & inhibitors; HeLa Cells; Heterocyclic Compounds - pharmacology; HIV Long Terminal Repeat; HIV replication; Human immunodeficiency virus; Humans; Imidazoisoindoles; Medical sciences; NF-kappa B - antagonists & inhibitors; NF-κB; Pharmacology. Drug treatments; Phthalazinones; Pyrimidoisoindoles; Stilbenes - pharmacology; Tat; NF-κB; Imidazoisoindoles; Tat; Benzalphthalides; HIV replication; Pyrimidoisoindoles; Phthalazinones; Transcription; RNA binding protein; Retroviridae; Virus replication cycle; Lentivirus; In vitro; Biological activity; Virus; Phthalazine derivatives; Cell line; Antiviral; Replication; Transcription factor NFκB; Inhibition; Human immunodeficiency virus; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.04.087

The inhibitory activity of several benzalphthalides, phthalazin-1-ones, imidazo[2,1- a]isoindoles and pyrimido[2,1- a]isoindoles on NF-κB, Tat and HIV replication is evaluated. Viral transcription has not been routinely targeted in the development of new antiviral drugs. This crucial step of the viral cycle depends on the concerted action of cellular and viral proteins such as NF-κB and Tat. In the present study, stilbene-related heterocyclic compounds including benzalphthalide, phthalazinone, imidazoindole and pyrimidoisoindole derivatives are tested for their anti-HIV activity. Original assays based on recombinant viruses were used to evaluate HIV replication inhibition and stably transfected cell lines were used to evaluate inhibition of Tat and NF-κB proteins. Some of the stilbene-related heterocyclic compounds analysed displayed anti-HIV activity through interference with NF-κB and Tat function. Moreover, compounds inhibiting both targets displayed a stronger activity on viral replication.