In vitro and in vivo activities of sedecamycin against Treponema hyodysenteriae

Hayashi, Tetsu; Suenaga, Itaru; Narukawa, Noriaki; Yamazaki, Toshiyuki

doi:10.1128/aac.32.4.458

Cited by 19 publications

(18 citation statements)

References 15 publications

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“…318–323 The acyclic substrate LC-KA05 ( 456 ) is formed by a hybrid NRPS-PKS assembly line with γ-lactone formation as the termination and product release step. 324 Concerted desaturation of the secondary amine to the product iminium ( 457 ) and capture by the enol carbon to create the new C-N bond that forms the 17 atom macrocycle lankacidinol A ( 458 ) is catalyzed by the enzyme LkcE (Scheme 64).…”

Section: Nonradical Cyclization Mechanismsmentioning

confidence: 99%

Oxidative Cyclization in Natural Product Biosynthesis

et al. 2016

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Oxidative cyclizations are important transformations that occur widely during natural product biosynthesis. The transformations from acyclic precursors to cyclized products can afford morphed scaffolds, structural rigidity and biological activities. Some of the most dramatic structural alterations in natural product biosynthesis occur through oxidative cyclization. In this review, we examine the different strategies used by Nature to create new intra-(inter-)-molecular bonds via redox chemistry. The review will cover both oxidation- and reduction-enabled cyclization mechanisms, with an emphasis on the former. Radical cyclizations catalyzed by P450, nonheme iron, α-KG dependent oxygenases and radical SAM enzymes are discussed to illustrate the use of molecular oxygen and S-adenosylmethionine to forge new bonds at unactivated sites via one-electron manifolds. Nonradical cyclizations catalyzed by flavin-dependent monooxygenases and NAD(P)H-dependent reductases are covered to show the use of two-electron manifolds in initiating cyclization reactions. The oxidative installation of epoxides and halogens into acyclic scaffolds to drive subsequent cyclizations are separately discussed as examples of “disappearing” reactive handles. Lastly, oxidative rearrangement of rings systems, including contractions and expansions will be covered.

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Section: Nonradical Cyclization Mechanismsmentioning

confidence: 99%

Oxidative Cyclization in Natural Product Biosynthesis

et al. 2016

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“…T. hyodysenteriae DJ70P3 (11), which is pathogenic in mice, was used. The inoculum was prepared as described previously (23 the probit method (17) from the rate at which T. hyodysenteriae was eradicated from the cecum.…”

Section: Methodsmentioning

confidence: 99%

“…By using this animal model, we have shown that orally administered sedecamycin, a 17-member macrocyclic antibiotic (Fig. 1), shows good efficacy in mice (11).…”

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confidence: 99%

Role of intestinal excretion in the effect of subcutaneously administered sedecamycin on cecal infection caused by Treponema hyodysenteriae in mice

Hayashi

Okada

Kondo

et al. 1991

Antimicrob Agents Chemother

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The therapeutic effects of subcutaneously administered sedecamycin on experimental Treponema hyodysenteriae infection in mice were evaluated. Sedecamycin was more active than tiamulin and lincomycin. The efficacy of sedecamycin upon subcutaneous administration was similar to that upon oral administration. Sedecamycin given subcutaneously provided similar degrees of protection in bile duct-ligated and intact mice. Pharmacokinetic studies utilizing a liquid chromatographic technique were carried out to determine the concentration of sedecamycin in the cecum, the site of T. hyodysenteriae infection in mice. Little sedecamycin was found; however, lankacidinol, a major metabolite of sedecamycin, was found in the cecal contents of intact mice after subcutaneous or oral administration of sedecamycin. Lankacidinol was also found in the cecal contents of bile duct-ligated mice, although the concentration found after subcutaneous administration of sedecamycin was much lower than that found after subcutaneous or oral administration to intact mice. These results indicate that sedecamycin is excreted directly into the intestinal tract as an active metabolite by a route other than the bile duct. It is suggested that this intestinal excretion plays an important role in the efficacy of subcutaneously administered sedecamycin against cecal infection of mice by T. hyodysenteriae.Treponema hyodysenteriae, the etiologic agent of swine dysentery, is characterized by mucohemorragic diarrhea (9,25). In general, severely infected animals are reluctant to consume the medicated feed. In such cases, parenteral administration of effective drugs, lincomycin (8) and tiamulin (1, 2), is used for treatment. Swine dysentery is infection with T. hyodysenteriae in the large intestine (5, 10); therefore, a sufficient amount of a drug must be distributed to the large intestine. When a drug is administered parenterally, the route by which it is distributed to the large intestine is thought to be biliary and intestinal excretion. Recently, intestinal excretion has become a well-recognized phenomenon (3,4,7,13,22). However, little is known about the pharmacokinetics of injectable drugs for swine dysentery in relation to efficacy.Experimental infection of mice and rabbits with T. hyodysenteriae had failed until Joens and Glock (14) reported that CF1 mice inoculated with T. hyodysenteriae for 2 consecutive days after a 72 h of fasting developed cecal and colonic lesions. Later, Suenaga and Yamazaki (24) reported that they examined mouse strains and found that Ta:CF#1 mice developed gross cecal lesions after a single oral administration of T. hyodysenteriae without fasting. By using this animal model, we have shown that orally administered sedecamycin, a 17-member macrocyclic antibiotic ( Fig. 1), shows good efficacy in mice (11).The objective of this study was to evaluate the efficacy of subcutaneous administration of sedecamycin against experimental infection of mice with T. hyodysenteriae and to explain the mechanisms of the efficacy by the concentra...

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“…Sedecamycin was developed in the authors' research laboratories and exhibited remarkable effects o n swine dysentery caused by Serpulina hyodysenteriae, not only in experimental swine infection models, but also in natural outbreaks in the field trials (YAMAZAKI et al, 1986;HAYASHI et al, 1988;TSUBOTA, 1989). Terdecamycin {(-)-N-[( lS, 2R, 7S, 13S, 15R, 19R)-(3E, 5E, 9E, 11E)-13-hydroxy-7-(4-methylpiperazino)carbonyloxy-1,4,10,19-tetramethyl-17,18-dioxo-16-oxabicyclo[l3.2.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Activity of Terdecamycin against Serpulina hyodysenteriae and Mycoplasma hyopneumoniae

Ueda

Hayashi

Narukawa

1994

Journal of Veterinary Medicine, Series B

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Terdecamycin is an antibacterial compound which is synthesized by chemically modifying sedecamycin. In this study, 51 and 53 field isolates of Serpulina hyodysenteriae and Mycoplasma hyopneumoniae, respectively, were examined for their susceptibility to terdecamycin. Terdecamycin showed a high activity against all isolates of S. hyodysenteriae and M . hyopneumoniae. Its activity against S. hyodysenteriae was higher than that of sedecamycin and its activity against M. hyopneumoniae was equivalent to that of tylosin, lincomycin and tiamulin. Chemically modifying sedecamycin potentiated the antibacterial activity and broadened its spectrum. P W 0

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In vitro and in vivo activities of sedecamycin against Treponema hyodysenteriae

Cited by 19 publications

References 15 publications

Oxidative Cyclization in Natural Product Biosynthesis

Oxidative Cyclization in Natural Product Biosynthesis

Role of intestinal excretion in the effect of subcutaneously administered sedecamycin on cecal infection caused by Treponema hyodysenteriae in mice

In Vitro Activity of Terdecamycin against Serpulina hyodysenteriae and Mycoplasma hyopneumoniae

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