Anti-Leishmanial Activity of Plant-Derived Acridones, Flavaglines, and Sulfur-Containing Amides

Abstract

Visceral and cutaneous leishmaniases are an important public health problem in endemic geographic regions in 88 countries worldwide, with around 12 million infected people. Treatment options are limited due to toxicity and teratogenicity of the available drugs, response problems in HIV/Leishmania co-infections, and upcoming resistances. In this study, we investigated the anti-leishmanial activity of 13 plant-derived compounds in vitro aiming to find new drug candidates. Toxicity of the compounds was evaluated in human primary hepatocytes, and hemolytic activity was examined in freshly isolated erythrocytes. Two acridones, 5-hydroxynoracronycine and yukocitrine, two flavaglines, aglafoline and rocaglamide, and the sulfur-containing amide methyldambullin showed promising anti-leishmanial activities with 50% effective concentrations (EC50s) of 34.84, 29.76, 7.45, 16.45, and 6.29 μM, respectively. Hepatotoxic activities of 5-hydroxynoracronycine, yukocitrine, and methyldambullin were significantly lower compared to miltefosine and lower or equal compared to artesunate, whereas the ones of rocaglamide and aglafoline were slightly higher compared to miltefosine and significantly higher compared to artesunate. None of the compounds showed hemolytic activity.

Activity of methylgerambullin from Glycosmis species (Rutaceae) against Entamoeba histolytica and Giardia duodenalis in vitro

“…It obeys Lipinski's “Rule of 5”, but it will be much more difficult to sythesize than methylgerambullin, as aglafoline possesses five centres of chirality. In our older studies it had shown activity against L. infantum (Astelbauer et al, 2011) and P. falciparum (Astelbauer et al, 2012), but not against T. cruzi .…”

“…Methylgerambullin had the lowest EC 50 of 2.83 μM after 48 h of treatment, compared to 4.50 μM and 4.17 μM for sakambullin and methyldambullin. In a second study on L. infantum promastigotes, methyldambullin had an EC 50 of 1.1 μM after 48 h of treatment (Astelbauer et al, 2011), and later, the activity of methylgerambullin after 48 h was tested at an EC 50 of 0.56 μM (Astelbauer, unpublished data).…”

“…(Rutaceae). These compounds were highly active in low micromolar concentrations against Trypanosoma cruzi epimastigotes (Astelbauer et al, 2010) and Leishmania infantum promastigotes (Astelbauer et al, 2011). In the present work we tested the activity of a similar set of 14 compounds against E. histolytica and G. duodenalis and found the sulphur-containing amide methylgerambullin to display the highest activity.…”

Olea europaea Bitki Ekstrelerinin Türkiye’den Elde Edilmiş Leishmania tropica İzolatına Antileishmanial Etkisinin Araştırılması

“…Avusturya'da 13 bitkiden elde edilen doğal bileşikler, in vitro antileishmanial aktivite yönünden araştırıl-mış, visseral ve kutanöz leishmaniasis tedavisi için yeni ilaçlara kaynak olabilecek bileşiklerin varlığı gösterilmiştir (27) .…”

Applications of Nanomaterials in Leishmaniasis: A Focus on Recent Advances and Challenges

“…With research advancements, several diagnostic and therapeutic lines have been developed against leishmaniasis. Among all forms of leishmaniasis, VL could be fatal as it affects the organs if not treated properly within two years [29,31]. The diagnosis of leishmaniasis is usually done by examination of the tissue of lesions under microscope.…”