Potent Antimalarial Activities of Polyether Antibiotic, X-206.

Otoguro, Kazuhiko; Kohana, Akiko; Manabe, Chizu; Ishiyama, Aki; Ui, Hideaki; Shiomi, Kazuro; Yamada, Hideaki; Ōmura, Satoshi

doi:10.7164/antibiotics.54.658

Cited by 96 publications

(92 citation statements)

References 16 publications

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“…Therefore, the remaining degree of unsaturation should be because of a ring structure. The HMBC correlations from the oxygenated sp 3 Figure 4. This structure was confirmed by the NOE correlations between the methoxy proton and H-7, and between H-3 and H 2 -8.…”

Section: Structure Elucidationmentioning

confidence: 99%

“…3 A mouse model using a malaria-derived strain of P. berghei N (chloroquine sensitive) was used to assess in vivo antimalarial activity, as described previously. 3,4 Test compounds were solubilized in 10% DMSO-Tween 80 aq. soln and administered s.c. to mice 2 h after infection with parasites (day 0).…”

Section: Assay Of Antimalarial Activity In Vitro and In Vivomentioning

confidence: 99%

“…[3][4][5][6][7][8] Recently, we have isolated some tropolone compounds from a culture broth of Penicillium sp. FKI-4410.…”

Section: Introductionmentioning

confidence: 99%

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In vitro and in vivo antimalarial activity of puberulic acid and its new analogs, viticolins A–C, produced by Penicillium sp. FKI-4410

et al. 2010

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In the course of screening for antimalarial agents, five tropolone compounds were isolated from the culture broth of Penicillium sp. FKI-4410. Two were known compounds, puberulic acid and stipitatic acid. Three were new analogs of puberulic acid, designated viticolins A-C. Among them, puberulic acid exhibited potent antimalarial inhibition, with IC 50 values of 0.01 lg ml À1 against chloroquine-sensitive and -resistant Plasmodium falciparum strains in vitro. Furthermore, puberulic acid showed weak cytotoxicity against human MRC-5 cells, with an IC 50 value of 57.2 lg ml À1 . The compound also demonstrated a therapeutic effect in vivo, which compared well against the currently used antimalarial drugs, and thus shows promise as a leading candidate for development into a new antimalarial compound.

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Section: Structure Elucidationmentioning

confidence: 99%

Section: Assay Of Antimalarial Activity In Vitro and In Vivomentioning

confidence: 99%

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In vitro and in vivo antimalarial activity of puberulic acid and its new analogs, viticolins A–C, produced by Penicillium sp. FKI-4410

et al. 2010

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“…[3][4][5][6][7][8] In the course of our screening, we found borrelidin, produced by an actinomycete strain OM-0060, that proved to be more potent than chloroquine or artemether (using in vivo oral administration) against drug-resistant P. yoelii. 6 The reported biological activities of borrelidin are suggested to be the results of protein synthesis inhibition, caused by the effect on threonyl-tRNA synthetase.…”

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confidence: 95%

“…11 However, the mechanism of antimalarial activity of borrelidin has not yet been identified. In this paper, we report the stage-specific action of borrelidin in vitro, using a drug-resistant parasite strain, determined by parasite lactate dehydrogenase (p-LDH) activity 3 and by morphological observation. Furthermore, we tested the effect of L-threonine, which appears to curtail the antimalarial activity of borrelidin, possibly through its effect on threonyl-tRNA synthetase, with a view to gaining an initial assessment of the antimalarial mode of action.…”

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Borrelidin, a potent antimalarial: stage-specific inhibition profile of synchronized cultures of Plasmodium falciparum

et al. 2011

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Polyether Antibiotics

Brimble

2003

Kirk-Othmer Encyclopedia of Chemical Technology

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Several polyether antibiotics have found commercial application as anticoccidials in poultry farming and in improvement of feed efficiency for ruminants. These antibiotics are characterized by multiple tetrahydrofuran and tetrahydropyran rings connected by aliphatic bridges, direct CC linkages, or spiro linkages. Other features include a free carboxyl function, many lower alkyl groups, and a variety of functional oxygen groups. These structural features enable transport of cations across lipid membranes. Some polyethers have found application as components in ion‐selective electrodes for use in clinical medicine or in laboratory studies involving transport studies or measurement of transmembrane electrical potential. The polyether class can be subdivided based on the number of carbon atoms in the backbone, ie, the longest chain of contiguous carbons between the carboxyl group and the terminal carbon. The 30 C skeleton group accounts for ∼60% of the polyethers for which structures have been determined. Monensin, widely used as an anticoccidial and feed efficiency enhancer, is an example of the 26 C backbone class. Maduramicin, another commercially important polyether, is shown as an example of the 30 C group with a sugar moiety. Many of the production procedures for polyethers utilize the separation of the mycelium followed by extraction using solvents such as methanol or acetone. A number of the polyethers can be readily crystallized. Polyethers such as monensin, lasalocid, salinomycin, and narasin are sold in many countries in crystalline or highly purified forms for incorporation into feeds or sustained‐release bolus devices. There are also mycelial or biomass products, especially in the United States, generally prepared by separation of the mycelium and then drying by azeotropic evaporation, fluid‐bed driers, or other types of commercial driers. Sophisticated methods have been developed for the chemical analysis of polyether antibiotics in feeds and residues that include the use of liquid chromatography–mass spectrometry (LCMS), bioautography, and enzyme‐linked immunosorbent assay (ELISA). The polyether antibiotics exhibit a broad range of biological, antibacterial, antifungal, antiviral, anticoccidial, antiparasitic, and insecticidal activities. They improve feed efficiency and growth performance in ruminant and monogastric animals. Only the anticoccidial activity in poultry and cattle, and the effect on feed efficiency in ruminants such as cattle and sheep, are of commercial interest. It is estimated that the polyether ionophores constitute > 80% of the total worldwide usage of anticoccidials. Bacteria belonging to the order Actinomycetales are the organisms reported to produce all of the polyethers. Most are secondary metabolites of Streptomyces sp. with the species hygroscopicus and albus accounting for about one‐third of the antibiotics. An alternative to the Cane‐Clemer‐Westley unified stereochemical model for the biosynthesis of polyether antibiotics via cyclization of polyepoxides has been proposed. The alternative model invokes construction of polyethers via hydroxyl‐directed syn oxidative polycyclization of a hydroxypolyene. Biosynthesis of polyether antibiotics is catalyzed by a large family of polyketide synthases (PKSs) that function in a similar manner to fatty acid synthase using malonyl‐CoA, methylmalonyl‐CoA, and ethylmalonyl‐CoA as extender units for building the polyketide backbone. Many gene clusters encoding the enzymes of polyketide biosynthesis have been cloned and characterized. Combinatorial biosynthesis provides a promising new approach of growing importance for the synthesis of hybrid “unnatural” antibotics by means of genetic engineering of recombinant strains bearing the biosynthetic genes of bacterial polyketide synthases. The polyether antibiotics provide a complex molecular framework for the development of new synthetic strategies for their total synthesis. Over 16 of the polyether antibiotics have succumbed to total synthesis. Monensin and salinomycin represent ∼ 65–70% of worldwide usage of polyether antibiotics for controlling coccidiosis. Lasalocid, narasin, and maduramicin make up the remainder. Other compounds for coccidiosis control include nicarbazine, halofunginone, amprolium, and robenidine.

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Potent Antimalarial Activities of Polyether Antibiotic, X-206.

Cited by 96 publications

References 16 publications

In vitro and in vivo antimalarial activity of puberulic acid and its new analogs, viticolins A–C, produced by Penicillium sp. FKI-4410

In vitro and in vivo antimalarial activity of puberulic acid and its new analogs, viticolins A–C, produced by Penicillium sp. FKI-4410

Borrelidin, a potent antimalarial: stage-specific inhibition profile of synchronized cultures of Plasmodium falciparum

Polyether Antibiotics

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