100587-52-8Relevant academic research and scientific papers
Synthesis and biological activity of new quinolone derivatives
Antonello,Uriarte,Palumbo,Valisena,Parolin,Palu
, p. 291 - 296 (1993)
A series of new quinolone derivatives bearing covalent modifications at the piperazine ring was synthesized and investigated for their biological properties. Two different types of substitutions at the level of the nitrogen at the 4' position were considered: introduction of a di- or tri-oxymethylene chain to modify steric hindrance and improve solubility in aqueous media or formation of a tertiary amide ending with a carboxylate group. In the latter case the net charge on the piperazine moiety changes from positive to negative at physiological conditions. In addition, a 'bis-quinolone' compound was examined, which lacks the piperazine ring and is also negatively charged at neutral pH. The new derivatives, except one, exhibited drug uptake, inhibition of DNA-gyrase activity and anti-bacterial potencies comparable to those of norfloxacin, and were modulation by the nature of the N4'-substituent. Besides indicating possible new modifications of the quinolone basic structure, the observation that substantially different substitution patterns at the same position did not cause impairment of biological activity suggests that the steric and electronic properties of this part of the molecule are not crucial for the recognition of DNA-gyrase.
Synthesis and activities of pyoverdin-quinolone adducts: A prospective approach to a specific therapy against Pseudomonas aeruginosa
Hennard,Que Chi Truong,Desnottes,Paris,Moreau,Abdallah
, p. 2139 - 2151 (2001)
Pseudomonas aeruginosa is particularly resistant to most all the antibiotics presently available, essentially because of the very low permeability of its outer membrane. To overcome this, we synthesized four siderophore-based antibiotics formed by two quinolones - norfloxacin and benzonaphthyridone - bound to the pyoverdin of P. aeruginosa ATCC 15692 via two types of spacer arms: one stable and the other readily hydrolyzable. From the comparison of their antibacterial properties with those of the two unbound quinolones, we reached the following conclusions: (a) The adducts inhibit Escherichia coli's gyrase showing that the dissociation of the compounds is not necessary for their activity. However, the presence of the pyoverdin moiety on the molecule decreases the inhibition activity compared to the antibiotic alone. (b) They facilitate the uptake of 55Fe using the specific pyoverdin-mediated iron-transport system of the bacterium. No uptake was observed either with P. aeruginosa ATCC 27853, which produces a structurally different pyoverdin, or with P. aeruginosa K690, which is a mutant of P. aeruginosa ATCC 15692 lacking FpvA, the outer-membrane pyoverdin receptor. (c) MIC determinations have shown that only strains P. aeruginosa ATCC 15692 and the derived outer-membrane receptor-producing but pyoverdin-deficient P. aeruginosa IA1 mutant present higher susceptibility to the pyoverdin-quinolone adducts, whereas P. aeruginosa ATCC 27853 and K690 are much more resistant. (d) Growth inhibition by these adducts confirmed these results and showed that the adducts with the hydrolyzable spacer arm have better activity than those with the stable one and that the labile spacer arm adducts present much higher activity than the quinolones alone. These results show clearly that the penetration of the antibiotic into the cells is favored when this latter is coupled with pyoverdin: Only the strains possessing the appropriate outer-membrane receptor present higher susceptibility to the adduct. In this case the antibiotic uses the pyoverdin-mediated iron-transport system. Furthermore, better efficiency is obtained when the spacer arm is labile and favors the antibiotic release inside the cell, allowing better inhibition of gyrase.
Synthesis and biological properties of conjugates between fluoroquinolones and a N3′′-functionalized pyochelin
Noel, Sabrina,Gasser, Veronique,Pesset, Benedicte,Hoegy, Franoise,Rognan, Didier,Schalk, Isabelle J.,Mislin, Gaetan L. A.
experimental part, p. 8288 - 8300 (2012/04/10)
Pyochelin is a siderophore common to Pseudomonas aeruginosa and several other pathogenic bacteria. A pyochelin functionalized at the N3′′ position with a propyl-amine extension was previously synthesized. In the present work we proved that this analog bin
Synthesis of pyochelin-norfloxacin conjugates
Rivault, Freddy,Liebert, Clemence,Burger, Alain,Hoegy, Francoise,Abdallah, Mohamed A.,Schalk, Isabelle J.,Mislin, Gaetan L.A.
, p. 640 - 644 (2007/10/03)
Using synthetic functionalized analogues of pyochelin, a siderophore common to several pathogenic Pseudomonas and Burkholderia species, four fluoroquinolone-pyochelin conjugates were efficiently synthesized and evaluated for their biological activities.
