RESUMEN
Schistosomiasis and soil-transmitted helminths are some of the priority neglected tropical diseases (NTDs) targeted for elimination by the World Health Organization (WHO). They are prevalent in Botswana and although Botswana has begun mass drug administration with the hope of eliminating soil-transmitted helminths as a public health problem, the prevalence of schistosomiasis does not meet the threshold required to warrant large-scale interventions. Although Botswana has a modern healthcare system, many people in Botswana rely on traditional medicine to treat worm infections and schistosomiasis. In this study, ten plant species used by traditional health practitioners against worm infections were collected and tested against Ancylostoma ceylanicum (zoonotic hookworm), Heligmosomoides polygyrus (roundworm of rodents), Necator americanus (New World hookworm), Schistosoma mansoni (blood fluke) [adult and newly transformed schistosomula (NTS)], Strongyloides ratti (threadworm) and Trichuris muris (nematode parasite of mice) in vitro. Extracts of two plants, Laphangium luteoalbum and Commiphora pyaracanthoides, displayed promising anthelmintic activity against NTS and adult S. mansoni, respectively. L. luteoalbum displayed 85.4% activity at 1 µg/mL against NTS, while C. pyracanthoides displayed 78.5% activity against adult S. mansoni at 10 µg/mL.
RESUMEN
Knipholone (1) and knipholone anthrone (2), isolated from the Ethiopian medicinal plant Kniphofia foliosa Hochst. are two phenyl anthraquinone derivatives, a compound class known for biological activity. In the present study, we describe the activity of both 1 and 2 in several biological assays including cytotoxicity against four human cell lines (Jurkat, HEK293, SH-SY5Y and HT-29), antiplasmodial activity against Plasmodium falciparum 3D7 strain, anthelmintic activity against the model organism Caenorhabditis elegans, antibacterial activity against Aliivibrio fischeri and Mycobacterium tuberculosis and anti-HIV-1 activity in peripheral blood mononuclear cells (PBMCs) infected with HIV-1c. In parallel, we investigated the stability of knipholone (2) in solution and in culture media. Compound 1 displays strong cytotoxicity against Jurkat, HEK293 and SH-SY5Y cells with growth inhibition ranging from approximately 62-95% when added to cells at 50 µM, whereas KA (2) exhibits weak to strong activity with 26, 48 and 70% inhibition of cell growth, respectively. Both 1 and 2 possess significant antiplasmodial activity against Plasmodium falciparum 3D7 strain with IC50 values of 1.9 and 0.7 µM, respectively. These results complement previously reported data on the cytotoxicity and antiplasmodial activity of 1 and 2. Furthermore, compound 2 showed HIV-1c replication inhibition (growth inhibition higher than 60% at tested concentrations 0.5, 5, 15 and 50⯵g/ml and an EC50 value of 4.3 µM) associated with cytotoxicity against uninfected PBMCs. The stability study based on preincubation, HPLC and APCI-MS (atmospheric-pressure chemical ionization mass spectrometry) analysis indicates that compound 2 is unstable in culture media and readily oxidizes to form compound 1. Therefore, the biological activity attributed to 2 might be influenced by its degradation products in media including 1 and other possible dimers. Hence, bioactivity results previously reported from this compound should be taken with caution and checked if they differ from those of its degradation products. To the best of our knowledge, this is the first report on the anti-HIV activity and stability analysis of compound 2.