YM‐216391, a Novel Cytotoxic Cyclic Peptide from Streptomyces nobilis. Part 1. Fermentation, Isolation and Biological Activities.

Sohda, Kin-ya; Nagai, Koji; Yamori, Takao; Suzuki, Kenichi; Tanaka, Akihiro

doi:10.1002/chin.200529194

Cited by 4 publications

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“…1), which was determined by a spectral analysis and chemical degradation to be a unique cyclic peptide. This peptide possessed potent cytotoxicity against human cancer cell lines in vitro, and is structurally related to mechercharstatin (2; former name, mechercharmycin), [1,2] and YM-216391 (3), [3,4] which are also potent cytotoxic compounds respectively isolated from the Thermoactinomycetaceae bacterium and Streptomyces. We describe in this paper the fermentation, isolation, and biological activities of 1.…”

Section: Introductionmentioning

confidence: 99%

Urukthapelstatin A, a Novel Cytotoxic Substance from Marine-derived Mechercharimyces asporophorigenens YM11-542

et al. 2007

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Urukthapelstatin A, a novel cyclic peptide, was isolated from the cultured mycelia of marine-derived Thermoactinomycetaceae bacterium Mechercharimyces asporophorigenens YM11-542. The peptide was purified by solvent extraction, silica gel chromatography, ODS flash chromatography, and finally by preparative HPLC. Urukthapelstatin A dose-dependently inhibited the growth of human lung cancer A549 cells with an IC 50 value of 12 nM. Urukthapelstatin A also showed potent cytotoxic activity against a human cancer cell line panel.

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Section: Introductionmentioning

confidence: 99%

Urukthapelstatin A, a Novel Cytotoxic Substance from Marine-derived Mechercharimyces asporophorigenens YM11-542

et al. 2007

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“…The structure of 1 was 257 [3,4] and telomestatin that has been isolated from Streptomyces anulatus [7]. This class of cyclic peptides containing a sequential oxazole-thiazole moiety represents a new group of antibiotics with highly potent activities.…”

Section: Discussionmentioning

confidence: 99%

“…The structure of 1 was 257 characterized as a cyclic peptide containing L-Ala, D-alloIle and a unique bioxazole-bithiazole-phenyloxazole moiety. Compound 1 is structurally related to the 24-membered cyclic compound, including mechercharstatin isolated from another Thermoactinomycetaceae bacterium [1,2], YM-216391 from Streptomyces nobilis [3,4] and telomestatin that has been isolated from Streptomyces anulatus [7]. This class of cyclic peptides containing a sequential oxazole-thiazole moiety represents a new group of antibiotics with highly potent activities.…”

Section: Discussionmentioning

confidence: 99%

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Urukthapelstatin A, a Novel Cytotoxic Substance from Marine-derived Mechercharimyces asporophorigenens YM11-542

et al. 2007

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The new cyclic peptide antibiotic, urukthapelstatin A, has been isolated from a culture of Thermoactinomycetaceae bacterium Mechercharimyces asporophorigenens YM11-542. The structure of urukthapelstatin A was elucidated by NMR, MS, Marfey analysis, chiral HPLC and X-ray crystal analyses. Keywords urukthapelstatin A, cyclic peptide, cytotoxic, Thermoactinomyces IntroductionUrukthapelstatin A (1) is a thiopeptide antibiotic which contains three oxazoles and two thiazoles in its cyclic structure and is structurally related to mechercharstatin (former name, mechercharmycin) [1,2] and YM-216391 [3, 4]. The fermentation, isolation and biological properties of 1 (Fig. 1) have been reported in the preceding paper [5]. This report describes the physico-chemical properties and structural determination of 1, which was produced by Mechercharimyces asporophorigenens YM11-542. Results Physico-chemical PropertiesThe physico-chemical properties of 1 are summarized in The relationship of the spin networks was established from 1 H-13 C long-range correlations in the HMBC spectrum and yielded three partial structures, which were assigned to a bithiazole-benzyloxazole moiety (C 15 H 7 N 3 OS 2 , partial structure A), one oxazole (C 3 HNO, partial structure B), and an alanine and isoleucinecontaining part (C 16 H 22 N 4 O 4 , partial structure C, Fig. 2). The HMBC correlations when n J CH was set to 2 Hz, were observed from H-34 (d H 8.59) to C-2 (d C 135.50), and from H-6 (d H 8.88) to C-4 (d C 155.11). Consequently, C-1 of partial structure A was connected to C-2 of partial structure B, and C-4 of partial structure B was connected to C-6 of partial structure C. In addition, the ROESY correlation of H-10 (d H 1.82) and N4-H (d H 9.49) revealed that a vinylmethyl part in partial structure C had a Z configuration (Fig. 2).Although there is no signal between partial structure A and C in HMBC spectrum, the C-20/C-21 connection can be brought about by the comparison of the molecular formula C 34 H 30 N 8 O 6 S 2 with a tolal of each partial structures (A; C 15 H 7 N 3 OS 2 , B; C 3 HNO, C; C 16 H 22 N 4 O 4 ), enabling the planer structure of 1 to be obtained.The absolute configuration of the alanine and isoleucine residues was determined by a Marfey analysis [6] and chiral HPLC analysis of the acid hydrolysate of 1. The Marfey analysis clarified the existence of L-Ala in the acid hydrolysate of 1, but D-Ile and D-allo-Ile were indistinguishable from the reversed-phase HPLC analysis of their FDAA derivatives. The chiral HPLC analysis successfully defined the absolute configuration of isoleucine as D-allo-Ile. Finally, the absolute stereochemistry of 1 was determined as shown in Fig. 1.An X-ray crystallographic analysis was also performed to confirm the full structure of 1. An adequate crystal was obtained by crystallization from CH 2 Cl 2 /MeOH (1 : 1). The crystal data and measurement conditions are summarized in the experimental section, and the ORTEP drawing shown in Fig. 3. The absolute configuration of 1 was ascertained ...

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“…1), which showed potent cytotoxicity against human cancer cell lines in vitro. The fermentation, isolation, and biological activities of 1 have been reported in the preceding paper [1]. This paper describes the physico-chemical properties and structure elucidation of 1.…”

Section: Introductionmentioning

confidence: 88%