The Isolation and Characterization of Three Crystalline Antibiotics from Streptomyces plicatus

Haskell, Theodore H.; Ryder, Albert; Frohardt, Roger P.; Fusari, Salvatore A.; Jakubowski, Zbigniew L.; Bartz, Quentin R.

doi:10.1021/ja01536a055

Cited by 48 publications

(8 citation statements)

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“…The extracts of broth filtrates and mycelia were subjected to ODS silica gel column chromatography followed by preparative HPLC separation, as described in the Experimental Section, to afford compounds 1 – 11 ( Figure 1 and Figure 2 ). Six known compounds were identified by their structures by comparing the spectroscopic data for 6 – 11 with those of the reported values for de-amosaminyl-cytosamine ( 6 ), plicacetin ( 7 ), bamicetin ( 8 ), amicetin ( 9 ), collismycin B ( 10 ), and SF2738 C ( 11 ), respectively [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”

Section: Resultsmentioning

confidence: 99%

“…M. smegmatis has been used most widely in the search for anti-mycobacterial substances due to its fast-growing and non-pathogenic properties [ 8 ]. Bioassay-guided isolation from the culture broth of strain TPU1236A yielded five new compounds, designated as streptcytosines A–E ( 1 – 5 ) ( Figure 1 ), together with six known compounds, de-amosaminyl-cytosamine ( 6 ) [ 9 ], plicacetin ( 7 ) [ 10 ], bamicetin ( 8 ) [ 11 , 12 , 13 ], amicetin ( 9 ) [ 9 , 11 , 12 , 13 ], collismycin B ( 10 ) [ 14 , 15 ], and SF2738 C ( 11 ) [ 15 ] ( Figure 2 ). The isolation and anti-mycobacterial activities of compounds 1 – 11 have been described in this study.…”

Section: Introductionmentioning

confidence: 99%

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Anti-Mycobacterial Nucleoside Antibiotics from a Marine-Derived Streptomyces sp. TPU1236A

Yamazaki

Ukai

et al. 2014

Marine Drugs

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Five new nucleoside antibiotics, named streptcytosines A–E (1–5), and six known compounds, de-amosaminyl-cytosamine (6), plicacetin (7), bamicetin (8), amicetin (9), collismycin B (10), and SF2738 C (11), were isolated from a culture broth of Streptomyces sp. TPU1236A collected in Okinawa, Japan. The structures of new compounds were elucidated on the basis of their spectroscopic data (HRFABMS, IR, UV, and 2D NMR experiments including 1H-1H COSY, HMQC, HMBC, and NOESY spectra). Streptcytosine A (1) belonged to the amicetin group antibiotics, and streptcytosines B–E (2–5) were derivatives of de-amosaminyl-cytosamine (6), 2,3,6-trideoxyglucopyranosyl cytosine. Compound 1 inhibited the growth of Mycobacterium smegmatis (MIC = 32 µg/mL), while compounds 2–5 were not active at 50 µg/disc. Bamicetin (8) and amicetin (9) showed the MICs of 16 and 8 µg/mL, respectively.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-Mycobacterial Nucleoside Antibiotics from a Marine-Derived Streptomyces sp. TPU1236A

Yamazaki

Ukai

et al. 2014

Marine Drugs

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“…[ 5 ] Thus far, over a dozen congeners of amicetin have been identified from natural sources including plicacetin, bamicetin, streptcytosines, and cytosaminomycins. [ 6‐12 ] Many of these amicetin‐type nucleosides also exhibit strong antibiotic activities against Gram‐positive bacteria and most notably against strains of Mycobacterium tuberculosis . In 2019, Ma et al .…”

Section: Background and Originality Contentmentioning

confidence: 99%

Total Synthesis of Nucleoside Antibiotics Amicetin, Plicacetin, and Cytosaminomycin A—D

2021

Chin. J. Chem.

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Main observation and conclusion Amicetin and congeners constitute a small family of complex pyrimidine nucleosides, which exhibit strong antibiotic activities against Gram‐positive bacteria and notably against strains of Mycobacterium tuberculosis. Herein, we report chemical synthesis of a series of disaccharide congeners of the amicetin family, including amicetin, plicacetin, and cytosaminomycin A—D. It is the first time for successful synthesis of amicetin, the prototypical member, and cytosaminomycins. The synthetic approach employs glycosyl N‐phenyltrifluoroacetimidate and thioglycoside donors to construct the characteristic aminodeoxydisaccharides consisting of α‐(1→4)‐glycosidic linkage, uses gold(I)‐catalyzed N‐glycosylation to furnish 2‐deoxy‐β‐nucleosides, and finally exploits amidation and global deprotection to complete the syntheses. It is noteworthy that the 3‐O‐protecting group in the 2‐deoxydisaccharide donors is found to be crucial for a successful N‐glycosylation to assemble the cytosaminomycin disaccharide nucleosides.

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“…Initially named sacromycin, this antibiotic was also identical to amicetin. The Upjohn group showed that the chemistry of amicetin included the acid- and base-catalyzed degradation of amicetin to produce, respectively, the fragments cytimidine and cytosamine. , Bamicetin and plicacetin (which lacks the α-methylserine) were subsequently isolated from S. plicatus . , Oxamicetin was isolated from Arthrobacter oxamicetus sp. and found to have slightly improved activity over amicetin against E. coli NIHJ (MIC = 25 vs 50 μg/mL) but was less active against S. aureus Smith (MIC = 12.5 vs 6.3 μg/mL).…”

Section: The Peptidylcytosine Antibioticsmentioning

confidence: 99%

Dissecting the Nucleoside Antibiotics as Universal Translation Inhibitors

2021

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Metrics & MoreArticle Recommendations CONSPECTUS: Without question, natural products have provided the lion share of leads, if not drugs themselves, for the treatment of bacterial infections. The bacterial arms race, fueled by selection and survival pressures has delivered a natural arsenal of small molecules targeting the most essential of life processes. Antibiotics that target these critical intracellular processes face the formidable defense of both penetrating a bacterial cell membrane and avoiding efflux to exert their effect. These challenges are especially effective in Gramnegative (Gram-(−)) bacteria, which have a double membrane structure and efficient efflux systems from the combination of outer-membrane porins and inner membrane proton pumps. In this landscape of offense and defense, our clinically used antibiotics have only successfully targeted three intracellular processes for therapeutic intervention in Gram-(−) bacteria: dihydrofolate biosynthesis, transcription, and translation. Not surprisingly, such critical survival machinery is a popular target for bacterial warfare, and eight of our 14 classes of commonly used antibiotics target translation with the bacterial ribosome remaining one the most vetted targets for antimicrobial therapy. On the plus side, its anionic character attracts cationic inhibitors, which are generally more capable of penetrating the bacterial cell wall, and clinical resistance rates are usually manageable as mutation of such a highly evolved machine is difficult. On the down side, this highly evolved machine renders it difficult to inhibit selectively, and the inhibition of prokaryotic translation versus both eukaryotic cellular and mitochondrial translation is critical for clinical development and minimization of undesired toxicities.A class of natural products known as the "nucleoside antibiotics" have historically been recognized as universal inhibitors of the ribosome and can inhibit translation in prokaryotes, eukaryotes, and archaea. While they have served an essential role in dissecting the biochemical underpinnings of the enzymatic functions of the ribosome, they have not proven therapeutically useful as they target the highly conserved rRNA in the P-site and are toxic to mammalian cells. In this Account, we describe our studies on the natural product amicetin, a nucleoside antibiotic that we have demonstrated to break the rule of being a universal translation inhibitor. While the cytosine of amicetin mimics C75 of the 3′-CCA tail of the P-site tRNA akin to other nucleoside antibiotics, we advance a hypothesis that amicetin's unique interaction with the ribosomal protein uL16 exploits an untapped mechanism for selectively targeting the bacterial ribosome. A complex molecule comprised of a nucleoside, carbohydrates and amino acids, amicetin is also chemically unstable. Our initial attempts to stabilize and simplify this scaffold are presented with the ultimate goal of rebuilding the compound with improved penetrance to bacterial cells. If successful, this scaffold ...

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The Isolation and Characterization of Three Crystalline Antibiotics from Streptomyces plicatus

Cited by 48 publications

References 1 publication

Anti-Mycobacterial Nucleoside Antibiotics from a Marine-Derived Streptomyces sp. TPU1236A

Anti-Mycobacterial Nucleoside Antibiotics from a Marine-Derived Streptomyces sp. TPU1236A

Total Synthesis of Nucleoside Antibiotics Amicetin, Plicacetin, and Cytosaminomycin A—D

Dissecting the Nucleoside Antibiotics as Universal Translation Inhibitors

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