Structure of pyrrolosine: a novel inhibitor of RNA synthesis, from the actinomycete Streptomyces albus

Ikegami, Susumu; Isomura, Haruhiko; Tsuchimori, Noboru; Osano, Yasuko T.; Hayase, T.; Yugami, Tomoko; Ohkishi, Haruyuki; Matsuzaki, Takao

doi:10.1021/ja00182a052

Cited by 18 publications

(5 citation statements)

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“…Although further studies are needed to establish the optimal 9DI dose regimen, the cumulative experience with this compound is sufficiently encouraging to consider exploring other purine nucleosides as anti-P. carinii agents. A recent report (17) that questioned the structure of 9DI has now been shown to be based on an erroneous structure assignment for "pyrrolosine," a naturally occurring C nucleoside that was isolated from culture filtrates of Streptomyces albus. Thus, the structure of 9DI has been reconfirmed as 1,5-dihydro-7-p-D-ribofuranosyl-4H-pyrrolo[3,2-d]pyrimidin-4-one, while "pyrrolosine" has been positively identified as the isomeric 4-aminofuro[3,2-d]pyrimidine C nucleoside (30).…”

Section: Discussionmentioning

confidence: 99%

Activities of antifolate, antiviral, and other drugs in an immunosuppressed rat model of Pneumocystis carinii pneumonia

Walzer

Foy

Steele

et al. 1992

Antimicrob Agents Chemother

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The efficacy of antifolate, antiviral, and other drugs was compared in an experimental model of pneumocystosis. Sulfamethoxazole (SMX) administered alone in doses of .60 mg/kg/day was highly effective in treatment and prophylaxis. Low (c15 mg/kg/day) doses of SMX showed limited, dose-related antiPneumocystis carinii activity in therapy but were more effective in prophylaxis. The dihydrofolate reductase (DHFR) inhibitors trimethoprim (TMP), pyrimethamine, and trimetrexate exhibited little anti-P. carinii activity when administered alone and did not enhance the efficacy of SMX; the effects of the DHFR inhibitors could not be related to the dose or the concentration in serum. These data suggested that the rat model is an excellent system for studying the anti-P. carinii activity of sulfonamides but is of limited value in studying DHFR inhibitors. The antiviral drugs azidothymidine, dideoxyinosine, inosine pranobex (Isoprinosine), amantadine, and acyclovir displayed little or no activity against P. carinii; however, azidothymidine did not impair the efficacy of SMX or TMP-SMX. These results supported the clinical practice of giving antiviral agents together with antifolate drugs to patients infected with human immunodeficiency virus and suggested that the beneficial effects of antiviral agents on the occurrence of pneumocystosis are due mainly to their effects on the virus or the host immune response. In contrast to the antiviral drugs, 9-deazainosine, a nucleoside analog with antiprotozoal properties, deinonstrated marked activity against P. carinii which was related to dose and route of administration. These data raised the possibility that anti-P. carinii activity is a general property of purine nucleosides Experimental studies of anti-P. carinii drugs have usually been performed in an immunosuppressed rat model of pneumocystosis, which is a reliable predictor of activity against the human form of the disease (10,13,20). In a previous study of antifolate drugs in this model (34), we found that anti-P. carinii activity was a general property of sulfonamides; these compounds were so effective that a doseresponse curve could not be established at the doses used. By contrast, DHFR inhibitors exhibited little anti-P. carinii activity and did not improve the efficacy of the sulfonamides * Corresponding author.or the sulfone dapsone. This lack of synergism differed from the results of previous workers (10,14,15) and raised questions about the value of using the rat model to screen antifolate drugs.In the present study, we have extended these observations by exploring the effect of lower doses of the sulfonamide sulfamethoxazole (SMX) in the therapy of experimental pneumocystosis. We

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Section: Discussionmentioning

confidence: 99%

Activities of antifolate, antiviral, and other drugs in an immunosuppressed rat model of Pneumocystis carinii pneumonia

Walzer

Foy

Steele

et al. 1992

Antimicrob Agents Chemother

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“…Special emphasis should be placed on a very unique furan-derivative: 3-acetamido-5-acetylfuran (3A5AF) available both from chitin and its monomeric sugar. − The uncommon substitution pattern on the furan ring cannot be easily achieved by conventional synthetic methods from petrochemicals but is an essential structural motif in compounds such as proximicin antibiotics, pyrrolosine and hyrtioseragamine A and B, all of which are molecules with biological activity. Since the development of one-step production of 3A5AF from chitin and its monomer, many pathways for the synthesis of derived compounds have been proposed and some of them were realized recently, creating a chemical space with a range of N-containing chemicals (Figure ).…”

Section: O-containing Chemicalsmentioning

confidence: 99%

Sustainable Routes for the Synthesis of Renewable Heteroatom-Containing Chemicals

Hülsey

Yang

Yan

2018

ACS Sustainable Chem. Eng.

158

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One of the biggest discrepancies between the structure of many utilized chemicals and petrochemicals is the ubiquity of heteroatoms in the former and the lack thereof in the latter. Many commodity chemicals and almost all specialty chemicals and pharmaceuticals contain one or more heteroatoms, but introducing functionalities containing oxygen, nitrogen, sulfur or phosphorus into crude oil-derived chemicals is often a very energy- and resource-intensive endeavor. This and the inevitable depletion of fossil resources in the not too distant future are the main reasons for the development of sustainable ways to produce compounds bearing heteroatoms. Synthesis of oxygen-containing compounds from renewable resources such as starch, cellulose and hemicellulose is already well-known, and the production of phenolic compounds from lignin is garnering significant attention recently. In the meantime, there is a surge in the valorization of chitin from waste crustacean and insect shells for the production of various nitrogen-containing compounds. Much less explored is the valorization of sulfur- and phosphorus-containing biomass components, although they find some high market value applications. Catalysis plays a central role to enable the conversion of biomass into value-added products with high activity and selectivity. Further developments made by chemical engineers and process technologists will be required to make those processes economically feasible and competitive with current synthetic schemes from fossil resources. This perspective highlights the most recent advances and the upcoming challenges in the development of renewable and sustainable routes toward heteroatom-containing chemicals.

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“…The immucillin compounds do not usually form adequate-quality crystals, and only adducts protonated on the aza-ribitol sugar (N1) positions have been reported (MILMAV: Federov et al, 2001;MEFZOM: Evans et al, 2000) (alphabetic codes used herein are those used in the Cambridge Structural Database, 2009). A related compound, with oxygen replacing NH in the saturated five-membered ring, is VOVJIZ (Otter et al, 1992), while compound VILHON (Ikegami et al, 1990) has been reassigned as a related 6 0 -amino compound by Otter et al (1992). Some of these compounds have been successfully defined 'in action' as inhibitors in sites within the enzymes (e.g.…”

Section: Commentmentioning

confidence: 99%

A synchrotron radiation study of the one-dimensional complex of sodium with (1S)-N-carboxylato-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol, a member of the 'immucillin' family

Gainsford¹,

Furneaux²,

Tyler³

et al. 2010

Acta Crystallogr C

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The sodium salt of [immucillin‐A–CO2H]− (Imm‐A), namely catena‐poly[[[triaquadisodium(I)](μ‐aqua)[μ‐(1S)‐N‐carboxylato‐1‐(9‐deazaadenin‐9‐yl)‐1,4‐dideoxy‐1,4‐imino‐d‐ribitol][triaquadisodium(I)][μ‐(1S)‐N‐carboxylato‐1‐(9‐deazaadenin‐9‐yl)‐1,4‐dideoxy‐1,4‐imino‐d‐ribitol]] tetrahydrate], {[Na2(C12H13N4O6)2(H2O)7]·4H2O}n, (I), forms a polymeric chain via Na+—O interactions involving the carboxylate and keto O atoms of two independent Imm‐A molecules. Extensive N,O—H...O hydrogen bonding utilizing all water H atoms, including four waters of crystallization, provides crystal packing. The structural definition of this novel compound was made possible through the use of synchrotron radiation utilizing a minute fragment (volume ∼2.4 × 10−5 mm−3) on a beamline optimized for protein data collection. A summary of intra‐ring conformations for immucillin structures indicates considerable flexibility while retaining similar intra‐ring orientations.

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Structure of pyrrolosine: a novel inhibitor of RNA synthesis, from the actinomycete Streptomyces albus

Cited by 18 publications

References 1 publication

Activities of antifolate, antiviral, and other drugs in an immunosuppressed rat model of Pneumocystis carinii pneumonia

Activities of antifolate, antiviral, and other drugs in an immunosuppressed rat model of Pneumocystis carinii pneumonia

Sustainable Routes for the Synthesis of Renewable Heteroatom-Containing Chemicals

A synchrotron radiation study of the one-dimensional complex of sodium with (1S)-N-carboxylato-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol, a member of the 'immucillin' family

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