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New phenazines were synthesized by oxygenation of 1- and 2-naphthol with transition metal peroxo complexes and in situ reaction with 1,2-diamines. The title compounds were evaluated for in vitro antimalarial activity against Plasmodium falciparum and chloroquine-resistant strains. Phenazines 12, 27, and 28 were most prominent in growth inhibition. In vivo protection against cerebral malaria was observed with the phenazines 11, 12, 20, and 27, whereas partial protection was provided by 19.

The study of the chemical constituents of the stem bark of Teclea afzelii (Rutaceae) has resulted in the isolation and characterization of four furoquinoline alkaloids, namely kokusaginine (1), tecleaverdoornine (2), maculine (3) and montrifoline (4) together with lupeol (5) and beta-sitosterol glucopyranoside (6). The structures of the isolated compounds were elucidated based on spectroscopic studies. The antimalarial activity of compounds 1-4 against Plasmodium falciparum in vitro shows partial suppression of parasitic growth.

Malaria, sleeping sickness, Chagas' disease, Aleppo boil, and AIDS are among the tropical diseases causing millions of infections and cases of deaths per year because only inefficient chemotherapy is available. Since the targeting of the enzymes of the polyamine pathway may provide novel therapy options, we aimed to inhibit the deoxyhypusine hydroxylase, which is an important step in the biosynthesis of the eukaryotic initiation factor 5A. In order to identify new lead compounds, piperidines were produced and biologically evaluated. The 3,5-diethyl piperidone-3,5-dicarboxylates 11 and 13 substituted with 4-nitrophenyl rings in the 2 and 6 positions were found to be active against Trypanosoma brucei brucei and Plasmodium falciparum combined with low cytotoxicity against macrophages. The corresponding monocarboxylates are only highly active against the T. brucei brucei. The piperidine oximether 53 demonstrated the highest plasmodicidal activity. Moreover, compounds 11 and 53 were also able to inhibit replication of HIV-1.

Eight compounds were isolated from the roots of Garcinia polyantha, and identified. Two of them, the xanthone garciniaxanthone I (1), and the triterpene, named garcinane (2), are reported as new natural products. The structures of the new compounds were elucidated on the basis of 1D and 2D NMR spectroscopic studies. The structure of compound 1 was confirmed by Xray crystallography. Among the remaining six known compounds, three were known xanthones [smeathxanthone A (3), smeathxanthone B (4), and chefouxanthone (5)], one benzophenone [isoxanthochymol (6)], one triterpene [magnificol], and one sterol [b -sitosterol]. The in vitro antimalarial activity of isoxanthochymol (6) against Plasmodium falciparum shows strong chemosuppression of parasitic growth.Keywords Garcinia polyantha, garciniaxanthone I, Xray crystallography, xanthones; antimalarial activity IntroductionThe genus Garcinia of the Guttiferae family is well known to be a rich source of bioactive prenylated xanthones [1ϳ3], triterpenes [4], and benzophenones [5,6]. In continuation of our search for bioactive substances from African medicinal plants, we investigated the methanol extract of the root bark of Garcinia polyantha, a tree distributed in the lowland tropical rainforest of West, East and Central Africa [7,8]. In the current investigation we focused on minor constituents from G. polyantha, and one new xanthone (1), one new triterpene (2), and six known compounds (3ϳ6, magnificol, and b -sitosterol), were isolated (Fig. 1). We report herein the structure elucidation of the eight natural products and their antimalarial activity. Materials and Methods General Experimental ProceduresMelting points were determined on a Büchi SMP-20 melting point apparatus and are uncorrected. UV spectra were measured with a UV-210 PC UV. IR spectra were recorded on a SHIMADZU FTIR-8400S spectrometer in KBr disks. EI-MS (ionization voltage 70 eV) and HR-EI-MS mass spectra were recorded on Finnigan MAT double focusing spectrometer Model 8230. 1 H-and 13 C-NMR spectra were recorded with a Bruker Avance 500 MHz NMR spectrometer in CDCl 3 or CDCl 3 /CD 3 OD. Chemical shifts are recorded relative to TMS (dϭ0) internal standard and coupling constants J are reported in Hz. Optical rotation were recorded with a Perkin-Elmer 241

Malaria is still a major cause of death in the tropics. There is an urgent need for new anti-malarial drugs because drug-resistant plasmodia frequently occur. Over recent years, we elucidated the biosynthesis of hypusine, a novel amino acid contained in eukaryotic initiation factor 5A (eIF-5A) in Plasmodium. Hypusine biosynthesis involves catalysis of deoxyhypusine synthase (DHS) in the first step of post-translational modification. In a screen for new inhibitors of purified plasmodium DHS, CNI-1493, a novel selective pro-inflammatory cytokine inhibitor used in clinical phase II for the treatment of Crohn's disease, inhibited the enzyme of the parasite 3-fold at a concentration of 2 microM. In vitro experiments with 200 microM CNI-1493 in Plasmodium-infected erythrocytes, which lack nuclei and DHS protein, showed a parasite clearance within 2 days. This can presumably be attributed to an anti-proliferating effect because of the inhibition of DHS by the parasite. The determined IC50 of CNI-1493 was 135.79 microM after 72 h. In vivo application of this substance in Plasmodium berghei ANKA-infected C57BL/6 mice significantly reduced parasitemia after dosage of 1 mg/kg or 4 mg/kg/body weight and prevented death of mice with cerebral malaria. This effect was paralleled by a decrease in serum TNF levels of the mice. We suggest that the new mechanism of CNI-1493 is caused by a decrease in modified eIF-5A biosynthesis with a downstream effect on the TNF synthesis of the host. From the current data, we consider CNI-1493 to be a promising drug for anti-malarial therapy because of its combined action, i.e., the decrease in eIF-5A biosynthesis of the parasite and host cell TNF biosynthesis.

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vis. -(EYONG, K. O.; FOLEFOC*, G. N.; KUETE, V.; BENG, V. P.; KROHN, K.; HUSSAIN, H.; NKENGFACK, A. E.; SAEFTEL, M.; SARITE, S. R.; HOERAUF, A.; Phytochemistry 67 (2006) 6, 605-609; Dep. Org. Chem., Univ. Yaounde, Yaounde, Cameroon; Eng.) -Lindner 26-157