Coumarin inhibitors of gyrase B with N -propargyloxy-carbamate as an effective pyrrole bioisostere

Periers, Anne-Marie; Laurin, Patrick; Ferroud, Didier; Haesslein, Jean‐Luc; Klich, Michel; Dupuis‐Hamelin, Claudine; Mauvais, Pascale; Lassaigne, Patrice; Bonnefoy, Alain; Musicki, Branislav

doi:10.1016/s0960-894x(99)00654-x

Cited by 33 publications

(15 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Novobiocin and coumermycin A 1 have been known to inhibit bacterial nucleic acid synthesis since the 1950s (Maxwell, 1997). Studies to elucidate the mechanism of action of coumarin antibiotics have revealed that they inhibit the ATP-dependent catalytic functions of DNA gyrase, such as DNA supercoiling and decatenation (Periers et al, 2000). This is achieved by competitive inhibition of ATP binding (Periers et al, 2000).…”

Section: Resultsmentioning

confidence: 99%

“…Studies to elucidate the mechanism of action of coumarin antibiotics have revealed that they inhibit the ATP-dependent catalytic functions of DNA gyrase, such as DNA supercoiling and decatenation (Periers et al, 2000). This is achieved by competitive inhibition of ATP binding (Periers et al, 2000). The addition of a prenyl group to the furanocoumarin skeleton results in an increase in lipophilicity of the molecule, facilitating its passage through the thick membrane of these bacteria to its target site.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The antimycobacterial constituents of dill (Anethum graveolens)

Stavri

Gibbons

2005

Phytother. Res.

View full text Add to dashboard Cite

As part of a project to characterize selected members of the Kuwaiti flora for their phytochemistry and antimycobacterial activity, a new furanocoumarin, 5-[4''-hydroxy-3''-methyl-2''-butenyloxy]-6,7-furocoumarin (3), was isolated from the whole herb of Anethum graveolens. The known compounds oxypeucedanin (1), oxypeucedanin hydrate (2) and falcarindiol (4) were also isolated from this plant. The structure of each compound was determined by interpretation of NMR and mass spectrometric data. The three known compounds exhibited antibacterial activity against a panel of rapidly growing mycobacteria with minimum inhibitory concentration (MIC) values in the range 2-128 microg/mL.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The antimycobacterial constituents of dill (Anethum graveolens)

Stavri

Gibbons

2005

Phytother. Res.

View full text Add to dashboard Cite

show abstract

“…In order to study the role of the 5-methyl-2-pyrrole carboxylate skeleton in this class of compounds, Musicki and co-workers [71] have introduced the N-propargyloxy carbamate moiety as an effective bio-isostere. Out of a series inactive as anti-microbial agents, when in association with ampicillin they brought down the MIC of ampicillin from 128 to 64µg/ml towards ampicillin-resistant S. aureus [77].…”

Section: Anti-microbial Activitymentioning

confidence: 99%

Recent Advances in Coumarins and 1-Azacoumarins as Versatile Biodynamic Agents

Kulkarni¹,

Kulkarni²,

Chao³

et al. 2006

CMC

225

View full text Add to dashboard Cite

Coumarins, also referred as benzopyran-2-ones, and their corresponding nitrogen counterpart, 1-azacoumarins also referred to as carbostyrils, are a family of nature-occurring lactones and lactams respectively. The plant extracts containing coumarin-related heterocycles, which were employed as herbal remedies in early days, have now been extensively studied for their biological activities. These investigations have revealed their potentials as versatile biodynamic agents. For example, coumarins with phenolic hydroxyl groups have the ability to scavenge reactive oxygen species and thus prevent the formation of 5-HETE and HHT in the arachidonic pathway of inflammation suppression. Recent in vivo studies have revealed the role of coumarins in hepatotoxicity and also in depletion of cytochrome P450. Similarly 1-azacoumarins which is part of quinoline alkaloids, are known for their diverse biological activity and recently, a 6-functionalized 1-aza coumarins are undergoing human clinical trials as an orally active anti-tumor drug in view of its farnesyl protein-inhibiting activity in the nanomolar range. Furthermore, several synthetic coumarins with a variety of pharmacophoric groups at C-3, C-4 and C-7 positions have been intensively screened for anti-microbial, anti-HIV, anti-cancer, lipid-lowering, anti-oxidant, and anti-coagulation activities. Specifically, coumarin-3-sulfonamides and carboxamides were reported to exhibit selective cytotoxicity against mammalian cancer cell lines. The C4-substituted aryloxymethyl, arylaminomethyl, and dichloroacetamidomethyl coumarins, along with the corresponding 1-azacoumarins, have been demonstrated to be potential anti-microbial and anti-inflammatory agents. To expand the structural diversity of synthetic courmarins for biological functions, attempts have also been made to attach a chloramphenicol side chain at C-3 position of courmarin. In addition, the bi- and tri-heterocyclic coumarins and 1-azacoumarins with benzofuran, furan and thiazole ring systems along with biocompatible fragments like vanillin have shown remarkable potency as anti-inflammatory agents in animal models. Photobiological studies on pyridine-fused polycyclic coumarins have highlighted their potential as thymine dimer photosensitisers and the structurally related compounds of both coumarin and carbostyrils have also been found to act via the DNA gyrase pathway in their anti-bacterial activity. Apart from the above works, the present review also addresses the potential roles of coumarins and carbostyrils as protease inhibitors, or fluorescent probes in mechanistic investigation of biochemical pathways, and their application for QSAR in theoretical studies. Though 1-Azacoumarins have received less attention as compared to coumarins in the literature, an attempt has been made to compare both the systems at various stages, so that it can spark new thoughts on synthetic methodologies, reactivity pattern and biological activities.

show abstract

“…Early investigations on structure-activity relationships among aminocoumarins (10,37) demonstrated that both ADHC and L-noviose are essential for antibacterial activity and that the substituents attached to these fragments have a significant impact on their bioactivities. Structurally modified aminocoumarins have been synthesized and investigated for their bioactivities with respect to that of novobiocin (6,16,17,27,29,30), and enhancement of the bioactivity of aminocoumarins while simultaneously improving their toxicological and pharmacological properties appears to be a realizable goal.…”

mentioning

confidence: 99%

Antimicrobial and DNA Gyrase-Inhibitory Activities of Novel Clorobiocin Derivatives Produced by Mutasynthesis

Galm¹,

Heller

Shapiro

et al. 2004

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Twenty-eight novel clorobiocin derivatives obtained from mutasynthesis experiments were investigated for their inhibitory activity towards Escherichia coli DNA gyrase and for their antibacterial activities towards clinically relevant gram-positive and gram-negative bacteria in comparison to novobiocin and clorobiocin. Clorobiocin was the most active compound both against E. coli DNA gyrase in vitro and against bacterial growth. All tested modifications of the 3-dimethylallyl-4-hydroxybenzoyl moiety reduced biological activity. The highest activities were shown by compounds containing a hydrophobic alkyl substituent at position 3 of the 4-hydroxybenzoyl moiety. Polar groups in this side chain, especially amide functions, strongly reduced antibacterial activity. Replacement of the alkyl side chain with a halogen atom or a methoxy group at the same position markedly reduced activity. Transfer of the pyrrole carboxylic acid moiety from O-3؆ to O-2؆ of L-noviose moderately reduced activity, whereas the complete absence of the pyrrole carboxylic acid moiety led to a loss of activity. Desclorobiocin derivatives lacking the chlorine atom at C-8 of the 3-amino-4,7-dihydroxycoumarin moiety also showed low activity. Lack of a methyl group at O-4؆ of L-noviose resulted in an inactive compound. From these findings it appears that clorobiocin represents a "highly evolved" structure optimized for bacterial transport and DNA gyrase inhibition.

show abstract

Coumarin inhibitors of gyrase B with N -propargyloxy-carbamate as an effective pyrrole bioisostere

Cited by 33 publications

References 18 publications

The antimycobacterial constituents of dill (Anethum graveolens)

The antimycobacterial constituents of dill (Anethum graveolens)

Recent Advances in Coumarins and 1-Azacoumarins as Versatile Biodynamic Agents

Antimicrobial and DNA Gyrase-Inhibitory Activities of Novel Clorobiocin Derivatives Produced by Mutasynthesis

Contact Info

Product

Resources

About