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

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 EC50 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.Figure optionsDownload as PowerPoint slideResearch highlights
► Berberine and its derivatives were evaluated for anti-HIV activity.
► Berberine showed an EC50 of 0.13 μM against HIV-1 NL4.3.
► Berberrubine showed better therapeutic index than berberine (EC50 2.8 μM, TI 60.42).
► Two berberine-9-O-esters showed better therapeutic index than berberine.