Design, synthesis, and structure–activity relationship studies of new phenolic DNA gyrase inhibitors

Lübbers, Thomas; Angehrn, Peter; Gmünder, Hans; Herzig, Silvia

doi:10.1016/j.bmcl.2006.12.065

Cited by 82 publications

(33 citation statements)

References 13 publications

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“…The docking energy of the Cinodine I, Cyclothialidine and Novobiocin were -09.14, -16.20 and -05.79 kcal/mol, respectively. The design and synthesis of a series of novel 2, 3-dihydroisoindol-1-ones structurally related to cyclothialidine 2 with DNA gyrase showed inhibition activity (Lübbers et al 2007). The fragment-based design of potent DNA gyrase inhibitors has been reported.…”

Section: Resultsmentioning

confidence: 99%

Gene network analysis of Aeromonas hydrophila for novel drug target discovery

2012

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Increasing the multi-drug resistance Aeromonas hydrophila creates a health problem regularly thus, an urgent needs to develop and screen potent antibiotics for controlling of the infections. There are many studies have focused on interactions between specific drugs, little is known about the system properties of a full drug interaction in gene network. Thus, an attractive approach for developing novel antibiotics against DNA gyrase, an enzyme essential for DNA replication, transcription, repair and recombination mechanisms which is important for bacterial growth and cell division. Homology modeling method was used to generate the 3-D structure of B subunit of DNA gyrase (gyrB) using known crystal structure. The active amino acids in 3-D structure of gyrB were targeted for structure based virtual screening of potent drugs by molecular docking. Number of drugs and analogs were selected and used for docking against gryB. The drugs Cinodine I, Cyclothialidine and Novobiocin were found to be more binding affinity with gyrB-drug interaction. The homology of gyrB protein sequence of A. hydrophila resembles with other species of Aeromonas closely showed relationship in phylogenetic tree. We have also demonstrated the gene network interactions of gyrB with other cellular proteins which are playing the key role in gene regulation. These findings provide new insight to understand the 3-D structure of gyrB which can be used in structure-based drug discovery; and development of novel, potent and specific drug against B subunit of DNA gyrase.

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Section: Resultsmentioning

confidence: 99%

Gene network analysis of Aeromonas hydrophila for novel drug target discovery

2012

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“…Coumarin and its derivatives have shown a diverse array of biological activities including antimicrobial [17], chemotherapeutic [18,19], anticoagulant [20] and antiinflammatory [21]. A number of both naturally occurring and synthetic coumarins including aminocoumarins [22,23], hydroxycoumarins [24,25], pyranocoumarins [26], and furanocoumarins [27] have been reported to have significant antimicrobial activity against a wide range of microbes. Following on from our previous work on a series of Ag(I) complexes of coumarin-3-carboxylates, which have proven antimicrobial activity and potential as effective biocides in hygienic coatings, a novel series of Ag(I) complexes of coumarin-4-carboxylates has been synthesised and screened for their antibacterial activity.…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterisation of silver(I) complexes of substituted coumarin-4-carboxylates which are effective against Pseudomonas aeruginosa biofilms

et al. 2014

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a b s t r a c tA novel series of coumarin-4-carboxylate ligands (2a-2l), their Ag(I) complexes (3a-3l) together with a number of their phenanthroline adducts (4d, 4f and 4g) have been synthesised and characterised. The ligands were prepared by either acid or base hydrolysis of their corresponding esters or by demethylation of a methylated acid derivative. The esters (1a-1i) were synthesised by an aromatic electrophilic substitution reaction between the conjugate base of substituted phenols and a vinyltriphenylphosphonium salt. The novel series of Ag(I) carboxylate complexes were prepared by reaction of silver nitrate with the coumarin ligands in aqueous/alcohol solution. The Ag(I) phenanthroline adducts were prepared by reaction of the Ag(I) complex with 1,10-phenanthroline in aqueous/alcohol solution. A selection of complexes were screened for their in vitro antibacterial activity against Pseudomonas aeruginosa grown planktonically or as a biofilm as well as a number of other clinically important strains, Escherichia coli, MRSA and Staphylococcus aureus. The activity against the P. aeruginosa biofilm was found to be significantly greater than against the planktonic bacteria.

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“…Серед них, зок-рема, доцільно відзначити 2-піролідиніл-5-тіооц-тові [1] та ізоіндоліл-3-тіооцтові [2][3][4] кислоти, які знайшли використання в ролі ключових бло-ків для конструювання конденсованих тіоазоци-нових структур -аналогів ізоіндолобензазоцино-вих алкалоїдів. У ряду похідних дигідробензо [f] ізохінолілтіооцтових кислот виявлені фунгіци-ди [5], 2,3-дигідроізоіндоліл-3-тіопропанових кис-лот -бактерицидні [6] та противірусні [7] аген-ти, а піролідиніл-2-тіокарбонових кислот -ам-незієвідновлюючі сполуки [8]. В контексті зазна-ченого вище не втрачає своєї актуальності про-блема спрямованої модифікації інших гетероци-клічних систем тіоалканкарбоксильними заміс-никами.…”

Section: Issn 2308-8303unclassified

Synthesis of 7-carboxyalkylthio-5,6,7,8-tetrahydro-1H-pyrazolo[3,4-e]diazepin-4-ones

Kemskiy

Bol’but

Вовк

2014

J. org. pharm. chem.

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which is based on the intramolecular cyclization of 5-amino-N-(2,2-dialkyloxyethyl)pyrazole-4-carboxamides in the solution of formic acid with thioalkan carboxylic acids. The synthesis of the starting 5-aminopyrazolo-4-carboxamides has been performed by condensation of 2-cyano-N-(2,2-dimethoxy)-3-dimetylaminoacryl(croton) amides with alkyl hydrazines or hydrolytic cleavage of 5-(2,2-dietoxyethyl)-1,5-dihydropyrazolo-4Н-[3,4-d]pirimidin-4-ones. The scheme of this reaction proposed involves the intramolecular cyclocondensation with the initial formation of the corresponding 7-hydroxy-5,6,7,8-tetrahydropyrazolo[3,4-e] -гидрокси-5,6,7,8-тетрагидропиразоло[3,4-e]

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Design, synthesis, and structure–activity relationship studies of new phenolic DNA gyrase inhibitors

Cited by 82 publications

References 13 publications

Gene network analysis of Aeromonas hydrophila for novel drug target discovery

Gene network analysis of Aeromonas hydrophila for novel drug target discovery

Isolation and characterisation of silver(I) complexes of substituted coumarin-4-carboxylates which are effective against Pseudomonas aeruginosa biofilms

Synthesis of 7-carboxyalkylthio-5,6,7,8-tetrahydro-1H-pyrazolo[3,4-e]diazepin-4-ones

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