Synthesis of 9-substituted derivatives of berberine as anti-HIV agents

• Published in: European journal of medicinal chemistry 2011-04, Vol.46 (4), p.1045-1049
• Main Authors: Bodiwala, Hardik S., Sabde, Sudeep, Mitra, Debashis, Bhutani, Kamlesh Kumar, Singh, Inder Pal
• Format: Article
• Language: English
• Subjects: Anti-HIV; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Anti-HIV Agents - toxicity; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Berberine; Berberine - analogs & derivatives; Berberine - chemical synthesis; Berberine - pharmacology; Berberine - toxicity; Berberrubine; Biological and medical sciences; Biological Products - chemistry; Cell Line; HIV Reverse Transcriptase - antagonists & inhibitors; HIV-1 - drug effects; HIV-1 - enzymology; Humans; Medical sciences; Pharmacology. Drug treatments; Reverse transcriptase
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2011.01.016

Naturally occurring protoberberine alkaloids, berberine and berberrubine along with 9-substituted derivatives of berberine were assessed for the anti-human immunodeficiency virus (HIV) activity. Berberine was found to be the most active compound with an EC 50 of 0.13 μM against HIV-1 NL4.3 virus in CEM-GFP cell lines. Berberrubine and two other compounds were found to be less active than berberine, at the same time they were less toxic than berberine. Enzyme based assay suggested that the anti-HIV activity of berberine and its analogs might be due to RTase inhibitory activity and some additional mechanisms. 9-Substituted derivatives of alkaloid berberine were evaluated against HIV-1 CEM-GFP cell lines. Two compounds were found to show better TI than berberine. Active compounds showed inhibition of HIV reverse transcriptase. [Display omitted] ► Berberine and its derivatives were evaluated for anti-HIV activity. ► Berberine showed an EC 50 of 0.13 μM against HIV-1 NL4.3. ► Berberrubine showed better therapeutic index than berberine (EC 50 2.8 μM, TI 60.42). ► Two berberine-9- O-esters showed better therapeutic index than berberine.