Synthesis and antibacterial activity of cephalosporins having a catechol in the C3 side chain.

Okita, Takaaki; Imae, Kiyoto; Hasegawa, Toshifumi; Iimura, Seiji; Masuyoshi, Shinji; Kamachi, Hajime; Kamei, Hideo

doi:10.7164/antibiotics.46.833

Cited by 12 publications

(2 citation statements)

References 9 publications

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“…Many catechol‐containing cephems (Fig. 7) were synthesized in the late 1980s and through the 1990s 27–45 . Like the catechol conjugates of the aminopenicillins, the cephem conjugates showed enhanced activity against Gram‐negative bacteria, especially P. aeruginosa and fairly ready evolution of resistance through loss of TonB or siderophore receptors, especially the catecholate‐siderophore receptors Cir and Fiu 46–48 .…”

Section: Synthetic Conjugates Between Siderophores and β‐Lactam Antibmentioning

confidence: 99%

“…7) were synthesized in the late 1980s and through the 1990s. [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] Like the catechol conjugates of the aminopenicillins, the cephem conjugates showed enhanced activity against Gram-negative bacteria, especially P. aeruginosa and fairly ready evolution of resistance through loss of TonB or siderophore receptors, especially the catecholatesiderophore receptors Cir and Fiu. [46][47][48] Gensberg et al suggested that a catechol conjugate of the 7␣-formamidocephem BRL41897A (30) was taken up via the pyochelin receptor FptA.…”

Section: Synthetic Conjugates Between Siderophores and ␤-Lactam Antibmentioning

confidence: 99%

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Siderophore conjugates

Page

2013

Annals of the New York Academy of Sciences

102

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There has been considerable effort expended in the investigation of the potential of siderophore conjugates of antibiotics to circumvent the permeability barrier imposed by the outer membrane of Gram-negative bacteria. There is also a small group of natural conjugates, the sideromycins. Among the synthetic analogues that have been investigated are conjugates of nucleosides, glycopeptides, macrolides, fluroquinolones, and, above all, β-lactams. Despite this effort, few compounds have progressed beyond experimental studies. One compound, the siderophore monosulfactam BAL30072, is in early clinical studies.

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Section: Synthetic Conjugates Between Siderophores and β‐Lactam Antibmentioning

confidence: 99%

Section: Synthetic Conjugates Between Siderophores and ␤-Lactam Antibmentioning

confidence: 99%

Siderophore conjugates

Page

2013

Annals of the New York Academy of Sciences

102

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β‐Lactam Antibiotics

Andreotti

Biondi

Modugno

2003

Burger's Medicinal Chemistry and Drug Discovery

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This chapter reviews the history of β‐lactams from the discovery of penicillin in 1928 to the more recently studied and the current trends in the field. The most relevant aspects related to the mechanism of action of β‐lactams are covered, and the various mechanisms of resistance to currently available β‐lactams that bacteria have adopted since the introduction of penicillin are described. A classification of β‐lactamases and their relevance in clinics is also provided. Applications of β‐lactams both in the hospital and in the community are reported, with particular attention to their pharmacokinetic properties, related side effects, and their therapeutic indications. The history and discovery of β‐lactams are described and all major classes are covered: penicillins, cephalosporins, oxacephems, carbacephems, penems, monobactams and nocardicins, carbapenems and trinems, classical (e.g., clavulanic acid, sulbactam, tazobactam), and the more recently disclosed β‐lactamase inhibitors. Several aspects related to the most recent developments in β‐lactams are also covered: new molecules active against difficult Gram‐positive strains or endowed with an antibacterial broad spectrum of action; potent orally active β‐lactams; injectable β‐lactams; and β‐lactamase inhibitors. The chapter concludes with a continuing analysis of the industry‐driven trends and the most recent new application of β‐lactams as inhibitors of protein export in bacteria. Finally, a few very interesting Web addresses and a comprehensive reference list are also provided.

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β‐Lactam Antibiotics

Testero

Fisher

Mobashery

2010

Burger's Medicinal Chemistry and Drug Discovery

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The β‐lactam classes of antibacterials are preeminent in the treatment of bacterial infection due to their unparalleled clinical efficacy and clinical safety. Following the discovery of the penicillins, successive β‐lactam drug discovery has added the cephalosporin, penem cephamycin, clavulanate, monobactam, nocardicin, and carbapenem subclasses. The driving force behind much of this era of discovery is the staggering ability of pathogenic bacteria to adapt previous generations of the β‐lactam by the acquisition and expression of resistance mechanisms. Although many factors contribute to β‐lactam resistance, alterations to the molecular targets of the β‐lactams (the penicillin binding proteins) and the use of enzymes (the β‐lactamases) capable of the hydrolytic deactivation of the β‐lactams are paramount. This review traces the historical development of β‐lactam drug discovery, with emphasis on the most recent progress in the medicinal chemistry, biochemistry, and microbiology of the β‐lactams leading to the discovery of new generation β‐lactam antibacterials effective against the Gram‐negative and ‐positive bacterial pathogens of current medical concern.

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Synthesis and antibacterial activity of cephalosporins having a catechol in the C3 side chain.

Cited by 12 publications

References 9 publications

Siderophore conjugates

Siderophore conjugates

β‐Lactam Antibiotics

β‐Lactam Antibiotics

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