Antiprotozoal screening of 60 South African plants, and the identification of the antitrypanosomal germacranolides schkuhrin I and II.

Two hundred and seven extracts were prepared from sixty plants from South Africa and screened for in vitro activity against Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum. For the 21 extracts which inhibited the growth of one or more parasites with more than 95 % at 10 µg/mL, the IC50 values against all four protozoal parasites and cytotoxic IC50 values against L6 myoblasts were determined. Amongst the most notable results are the activities of Psoralea pinnata (IC50 of 0.15 µg/mL), Schkuhria pinnata (2.04 µg/mL), and Vernonia mespilifolia (1.01 µg/mL) against Trypansoma brucei rhodesiense. HPLC-based activity profiling was used to identify the active constituents in the extracts, and the germacranolide sesquiterpene lactones schkuhrin I and II from S. pinnata, and cynaropicrin from V. mespilifolia were identified, with IC50 values of 0.9, 1.5, and 0.23 µM, respectively.

Mokoka TA ，Xolani PK ，Zimmermann S ，Hata Y ，Adams M ，Kaiser M ，Moodley N ，Maharaj V ，Koorbanally NA ，Hamburger M ，Brun R ，Fouche G ... -  《-》

Antiprotozoal Sesquiterpene Lactones and Other Constituents from Tarchonanthus camphoratus and Schkuhria pinnata.

Kimani NM ，Matasyoh JC ，Kaiser M ，Brun R ，Schmidt TJ ... -  《-》

In vitro screening of traditional South African malaria remedies against Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum.

Three hundred extracts were prepared from plants traditionally used in South Africa to treat malaria and screened in vitro for activity against Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum. For the 43 extracts which inhibited the growth of one or more parasites to more than 95 % at 9.7 µg/mL, the IC₅₀ values against all four protozoal parasites and cytotoxic IC₅₀s against rat myoblast L6 cells were determined. Amongst the most notable results are the activities of AGATHOSMA APICULATA (IC₅₀ of 0.3 µg/mL) against Plasmodium falciparum, as well as Salvia repens and Maytenus undata against Leishmania donovani with IC₅₀s of 5.4 µg/mL and 5.6 µg/mL, respectively. This screening is the starting point for a HPLC-based activity profiling project in antiprotozoal lead discovery.

Mokoka TA ，Zimmermann S ，Julianti T ，Hata Y ，Moodley N ，Cal M ，Adams M ，Kaiser M ，Brun R ，Koorbanally N ，Hamburger M ... -  《-》

The antiprotozoal activity of sixteen asteraceae species native to Sudan and bioactivity-guided isolation of xanthanolides from Xanthium brasilicum.

In vitro screening of the dichloromethane extracts of 16 Asteraceae species native to Sudan for activity against major protozoan pathogens revealed that a Xanthium brasilicum Vell. [syn. X. strumarium var. brasilicum (Vell.) Baker in Mart.] extract was the most active against Trypanosoma brucei rhodesiense, the etiological agent of East African human trypanosomiasis (IC(50) = 0.1 microg/mL). This plant extract also exhibited noticeable activities against T. cruzi (Chagas disease), Leishmania donovani (Kala-Azar) as well as Plasmodium falciparum (Malaria tropica). Bioactivity-guided fractionation resulted in the isolation of four bioactive sesquiterpene lactones (STL) of the xanthanolide series (4,5-seco-guaianolide-type). They were identified by spectroscopic means as 8-epixanthatin (1), 8-epixanthatin 1beta,5beta-epoxide (2), and as the dimers pungiolide A (4) as well as pungiolide B (5). Two further modified xanthanolide sesquiterpene lactones, xanthipungolide (3) and 4,15-dinor-1,11(13)-xanthadiene-3,5beta:12,8beta-diolide (6) were isolated. While xanthipungolide turned out to be inactive against the tested parasites, the dinor-xanthanlide showed significant activity against T. brucei rhodesiense and L. donovani. All isolated compounds were previously known from other Xanthium species but this is the first report on their occurrence in X. brasilicum, and, most notably, on their antiprotozoal activity. As the most active single compound from this extract, 8-epixanthatin 1beta,5beta-epoxide showed IC(50) values of 0.09, 2.95, 0.16 and 1.71 microg/mL (0.33, 11.3, 0.6 and 6.5 microM) against T. brucei rhodesiense, T. cruzi, L. donovani and P. falciparum, respectively, while its cytotoxicity against rat myoblast cells used as control was determined at 5.8 microg/mL (22.1 microM). Besides assessment of their antiprotozoal activity, the structural assignments for the dimeric xanthanolides pungiolide A and B were reinvestigated and fully established.

Nour AM ，Khalid SA ，Kaiser M ，Brun R ，Abdallah WE ，Schmidt TJ ... -  《-》

Antiprotozoal activity of Khaya anthotheca, (Welv.) C.D.C. a plant used by chimpanzees for self-medication.

Khaya species, endemic to Africa and Madagascar, continues to be valuable in indigenous traditional medicine. Their bitter tasting barks are decocted to treat fevers, several febrile conditions, microbial infections and worm infestations. In the Budongo rain forest of Western Uganda, non-human primates, especially chimpanzees and baboons, have been observed to eat the bitter non-nutritious bark and occasionally the seed. Extracts were prepared by sequential fractionation with solvents of increasing polarities and assayed using standard procedures. Bioassay guided purification of the petroleum ether extract by column chromatography yielded three pure limonoids, Grandifolione (1), 7-deacetylkhivorin (2) and 1,3-deacetyldeoxyhavenensin (3). The antitrypanosomal, antileishmanial and antiplasmodial activities of pure compounds (1) and (2) were evaluated in vitro against Plasmodium falciparum K1, Trypanosoma brucei rhodesiense STIB 900, Trypanosoma cruzi trypomastigotes (Tulahuen C4), and axenic Leishmania donovani MHOMET-67/L82 and for cytotoxicity against L6 rat skeletal myoblast cells, in parallel with standard drugs. Of the four extracts tested, the petroleum ether extract showed activity against Plasmodium falciparum (IC50 0.955 μg/ml) and Trypanosoma brucei rhodesiense (IC50 5.72 μg/ml). The pure compounds (1) and (2) demonstrated activity against Plasmodium falciparum (KI strain) and marginal activities against Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani. The present study provides evidence justifying the use of Khaya preparations in traditional medicine to treat fevers and microbial infections. The observed antiprotozoal activity of grandifolione and 7-deacetylkhivorin from the seed of Khaya anthotheca further confirms the ethnomedicinal potential of this plant and supports the hypothesis that non-human hominids (chimpanzees and baboons) too, eat the bitter bark and seeds for self-medication and in general, the use of Khaya plant material for medication by humans in disease endemic tropical areas. The antiprotozoal activity of gradifolione, and, the antitrypanosomal and antileishmanial activities of 7-deacetylkhivorin are reported here for the first time.

Obbo CJ ，Makanga B ，Mulholland DA ，Coombes PH ，Brun R ... -  《-》