Synthesis and Potent Antimalarial Activity of Kalihinol B

Of the 50+ kalihinane diterpenoids reported to date, only five had been tested for antimalarial activity, in spite of the fact that kalihinol A is the most potent among the members of the larger family of antimalarial isocyanoterpenes. We have validated a strategy designed to access many of the kalihinanes with a 12-step enantioselective synthesis of kalihinol B, the tetrahydrofuran isomer of kalihinol A (a tetrahydropyran). Kalihinol B shows similarly high potency against chloroquine-resistant Plasmodium falciparum

Boletín de Segovia: Número 96 - 1853 agosto 17

Copia digital. Madrid : Ministerio de Cultura. Subdirección General de Coordinación Bibliotecaria, 200

Additional file 1: Figure S1. of Analysis of nucleosome positioning landscapes enables gene discovery in the human malaria parasite Plasmodium falciparum

Supervised machine learning approach for novel gene detection. Figure S2. Optimization of classifier parameters. Table S1. Classifier performance and measurements. Figure S3. Density plots of various characteristics of predicted gene regions versus intergenic regions and annotated coding and non-coding genes in P. falciparum. Figure S4. Coverage profile of histone variants around gene boundaries. (PDF 1149 kb

Additional file 3: of The mRNA-bound proteome of the human malaria parasite Plasmodium falciparum

Document containing supplementary Figures S1–S10 and their legends. (PDF 1225 kb

Isodon trichocarpus Kudo

原著和名: クロバナヒキオコシ科名: シソ科 = Labiatae採集地: 長野県 白馬岳 (信濃 白馬岳)採集日: 1963/8/22採集者: 萩庭丈壽整理番号: JH042870国立科学博物館整理番号: TNS-VS-99287

In vivo activity of salinosporamide A against Rodent malaria parasite, <i>P. yoellii</i>.

<p>Mice were treated using 3 independent delivery methods: A) Intraperitoneal B) Oral Route and C) Subcutaneous. Mice treated by oral route at 250 µg/kg (<i>t</i>-test, <i>p</i> = 0.062) or by intra peritoneal and subcutaneous methods at 130 µg/kg showed a significant decrease of parasitemia when compared with control mice (<i>p</i><0.001). Parasitemia was almost cleared when used at 130 µg/kg when delivered by subcutaneous method (<i>p</i><0.001). Values are means±standard deviation.</p

Farnesides A and B, Sesquiterpenoid Nucleoside Ethers from a Marine-Derived <i>Streptomyces</i> sp., strain CNT-372 from Fiji

Farnesides A and B (<b>1</b>,<b> 2</b>), linear sesquiterpenoids connected by ether links to a ribose dihydrouracil nucleoside, were isolated from a marine-derived <i>Streptomyces</i> sp., strain CNT-372, grown in saline liquid culture. The structures of the new compounds were assigned by comprehensive spectroscopic analysis primarily involving 1D and 2D NMR analysis and by comparison of spectroscopic data to the recently reported ribose nucleoside JBIR-68 (<b>3</b>). The farnesides are only the second example of this exceedingly rare class of microbial terpenoid nucleoside metabolites. Farneside A (<b>1</b>) was found to have modest antimalarial activity against the parasite <i>Plasmodium falciparum</i>

Inhibition of <i>P. falciparum</i> growth by proteasome inhibitors and standard antimalarial drugs with their chemical structures.

<p>IC₅₀ values of parasite treated with the drug were determined using the SYBR Green assay and calculated by non linear regression using four-parameter logistic curves on SigmaPlot 10.0 software (values are mean±standard error of the mean). Each value in the curve is the average of 2 different experiments±standard deviation. Salinosporamide A inhibited the proliferation of the parasite at a low nanomolar range (IC₅₀ = 11.4±1.9 nM) suggesting that the compound is as efficient as standard antimalarials (e.g. chloroquine (2.3±0.15 nM), mefloquine (3.9±2.7 nM) and artemisinin (11.7±8.7 nM). The inhibitor MG-132 is also a potent inhibitor of the parasites growth <i>in vitro</i> (IC₅₀ of 40±4.8 nM) suggesting a strong inhibition effect of general proteasome inhibitors. Correlation coefficients (<i>R</i> values-factor of regression calculated by SigmaPlot 10.0) were 0.9887 for Sal A, 0.9996 for chloroquine, 0.9989 for mefloquine, 0.9900 for artemisinin and 0.9962 for MG-132.</p

Figure 5

<p>(A) Sequence alignment of the catalytic domain of the β5 subunit 20 S proteasome from yeast, human and <i>Plasmodium</i> obtained with the ClustalW program. (B) Crystal structure of Salinosporamide A interacting with the yeast 20S proteasome. Tyr168 is shown in orange to indicate the site of the Y168G mutation in <i>P. falciparum.</i></p

Inhibition effect of salinosporamide A on chloroquine resistant <i>P. falciparum</i> strain FCB.

<p>IC₅₀ values of parasite treated with the drug were determined using the SYBR Green assay. Each value in the curve is the average of 2 different experiments±standard deviation. Salinosporamide A inhibited the proliferation of the FCB strain suggesting that the compound is equally active against drug resistant parasites. IC₅₀ values with Salinosporamide A were 11.4 nM±1.9 for 3D7 (<i>R</i> = 0.9887) and 19.6 nM±1.4 for FCB (<i>R</i> = 0.9990). Chloroquine IC₅₀ values were 2.3 nM±0.15 (<i>R</i> = 0.9996) and 64.1 nM±4.7 (<i>R</i> = 0.9964) for 3D7 and FCB respectively.</p