Structure-activity relationship in two series of aminoalkyl substituted coumarin inhibitors of gyrase B

Laurin, Patrick; Ferroud, Didier; Schio, Laurent; Klich, Michael; Dupuis‐Hamelin, Claudine; Mauvais, Pascale; Lassaigne, Patrice; Bonnefoy, Alain; Musicki, Branislav

doi:10.1016/s0960-894x(99)00492-8

Cited by 52 publications

(32 citation statements)

References 28 publications

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“…Introduction of a basic side chain at the allylic position with respect to the biogenetically important C3-C4 double bond [17] was attempted to reduce the acidic character of coumarin antibiotics. Amongst the various alkyl amines and sulfides synthesized, the 4-piperazinomethyl and imidazomethyl sulfides [18] were found to be the most active compounds. We have been studying structurally analogous, 4-arylaminomethyl [19] 4-sulphonamidomethyl [20] and 4-dichloroacetamidomethyl coumarins [21] for their anti-bacterial activity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and antimicrobial studies on novel sulfonamides containing 4-azidomethyl coumarin

Basanagouda

Shivashankar

Kulkarni

et al. 2010

European Journal of Medicinal Chemistry

153

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a b s t r a c tA series of new and novel coumarin-6-sulfonamides with a free C4-azidomethyl group have been synthesized as antimicrobials in three steps starting from 7-methyl-4-bromomethylcoumarin 1. The reaction of 1 with chlorosulfonic acid was found to yield the corresponding 6-sulfonylchloride 2, which when treated with sodium azide led to intermediate 3. The title sulfonamides 5a-y were obtained from the reaction of 3 with various aromatic amines 4 in refluxing benzene. The chemical structures of the compounds were elucidated by IR, NMR and LC-MS spectral data. All the synthesized compounds have been screened for their in vitro anti-bacterial and anti-fungal activities. Some of the compounds have been found to be active against both bacterial species at a concentration of 1 mg/mL.

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Section: Introductionmentioning

confidence: 99%

Synthesis and antimicrobial studies on novel sulfonamides containing 4-azidomethyl coumarin

Basanagouda

Shivashankar

Kulkarni

et al. 2010

European Journal of Medicinal Chemistry

153

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“…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

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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.

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“…The largest peak in the final difference electron density synthesis was 0.148 e − /Å 3 and the largest hole was −0.136 e − /Å 3 with an RMS deviation of 0.029 e − /Å 3 . On the basis of the final model, the calculated density was 1.283 g/cm 3 and F(000), 552 e − .…”

Section: Crystal Structurementioning

confidence: 99%

“…Varieties of 4-substituted coumarins possessing hydroxyl [2], aminoalkyl [3] arylaminomethyl [4] sulphonamido [5] and aryloxymethyl [6] groups have exhibited anti coagulant, anti microbial and anti inflammatory activities. Coumarin 4-acetic acids have been found to exhibit good inflammation inhibiting activity in animal models [7].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Spectroscopic and Crystal Structure Studies on Ethyl 5,7-Dimethyl Coumarin-4-Acetate

Pujar¹,

Anilkumar²,

Kulkarni³

2013

CSTA

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Structure-activity relationship in two series of aminoalkyl substituted coumarin inhibitors of gyrase B

Cited by 52 publications

References 28 publications

Synthesis and antimicrobial studies on novel sulfonamides containing 4-azidomethyl coumarin

Synthesis and antimicrobial studies on novel sulfonamides containing 4-azidomethyl coumarin

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

Synthesis, Spectroscopic and Crystal Structure Studies on Ethyl 5,7-Dimethyl Coumarin-4-Acetate

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