Screening of Anthocleista djalonesis Fractions and Compounds against HIV-1 Integrase and HIV-1 Protease

Abstract

Aim: HIV, the virus that causes AIDS, is one of the world’s deadliest diseases today. Drug resistance and narrow spectrum of available therapeutics is a main problem during HIV treatment. Therefore, new drugs effective against drug-resistant HIV strains are needed. The aim of this study was to screen Anthocleista djalonensis extracts, fractions and isolated compounds for in vitro anti-HIV-1 Integrase (HIV-1 IN) and HIV-1 Protease (HIV -1 PR) activities. Place and Duration of Study: The study was carried out in the Department of Organic Chemistry, Rhodes University, Grahamstown, South Africa. The period was between March and July, 2016. Methodology: The ethyl acetate and acetone extracts of the roots of Anthocleista djalonensis and fractions and compounds obtained from column chromatography of acetone extract were screened for their inhibitory activity against HIV -1 Integrase using a non-radioactive ELISA-based HIV-1 integrase assay. The screening was carried out at concentration range of 10-5 -102 μg/ml. The screening for anti-protease activity was performed using a fluorogenic octapeptide substrate, HIV-FRET (1) and a recombinant HIV-1 Protease solution.  Results: The ethyl acetate and acetone extracts showed inhibitory effects on HIV -1 Integrase with IC50 of 1.3001 ± 0.217 µg/mL and 0.7216 ± 0.0028 µg/mL respectively. IC50 values of 0.0077 ± 0.009 µg/mL, 5.0001± 0.1719 µg/mL, 3.5113 ± 0.3613 µg/mL and 0.0736 ± 0.0005 µg/ml were obtained for chromatographic fractions F-1, F-2, F-3 and F-4 respectively. The compounds Bauerenone, Bauerenol and a mixture of Stigmasterol and β-Sitosterol isolated from A. djalonensis had IC50 values of 5.6112 ± 0.8767 µg/mL, 4.8075 ± 0.0732 µg/mL and 0.8916 ± 0.0327 respectively. Conclusion: Bauerenone, Bauerenol and a mixture of Stigmasterol and β-Sitosterol isolated from A. djalonensis showed significant (P< 0.05) inhibitory activities against HIV-1 Integrase. However, there was no activity against HIV-1 protease at 50 µg/mL by the extracts, fractions and isolated compounds.