HIV-1 protease and HIV-1 integrase inhibitory substances from Eclipta prostrata.
The bioassay-guided fractionation for anti-HIV-1 integrase activity led to the isolation of six compounds from the whole plant extract of Eclipta prostrata extract. They were identified as 5-hydroxymethyl-(2,2':5',2'')-terthienyl tiglate (1), 5-hydroxymethyl-(2,2':5',2'')-terthienyl agelate (2), 5-hydroxymethyl-(2,2':5',2'')-terthienyl acetate (3), ecliptal (4), orobol (5) and wedelolactone (6). Of these, compound 6 showed the highest activity against HIV-1 integrase (IN) with an IC50 value of 4.0+/-0.2 microm, followed by compound 5 (IC50=8.1+/-0.5 microm), whereas the four terthiophene compounds (1-4) were inactive (IC50>100 microm). Regarding HIV-1 protease (PR) inhibitory activity, compound 1 exhibited appreciable activity against HIV-1 PR with an IC50 of 58.3+/-0.8 microm, followed by compound 4 (IC50=83.3+/-1.6 microm) and compound 3 (IC50=93.7+/-0.8 microm), while compounds 2, 5 and 6 were inactive against HIV-1 PR (IC50>100 microm). This is the first report of anti-HIV-1 IN activities for wedelolactone (6), a coumarin derivative, and orobol (5), an isoflavone derivative. This study supports the use of E. prostrata in AIDS patients, which is in accord with its traditional use by Thai traditional doctors for curing blood related diseases.
Tewtrakul
Supinya
S
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla, 90112, Thailand. supinyat@yahoo.com
Subhadhirasakul
Sanan
S
Cheenpracha
Sarot
S
Karalai
Chatchanok
C
D019380:Anti-HIV Agents / Q000302:isolation & purification* / Q000494:pharmacology; D036601:Eclipta / Q000737:chemistry*; D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000302:isolation & purification; D016333:HIV Protease / Q000187:drug effects*; D017320:HIV Protease Inhibitors / Q000302:isolation & purification; D006801:Humans; D020128:Inhibitory Concentration 50; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry; D013785:Thailand
D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D010936:Plant Extracts; D019427:HIV Integrase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1; C514801:p31 integrase protein, Human immunodeficiency virus 1