&amp;#946;-Lactamases and their Inhibitors: An Update

Micetich, Ronald G.; Salama, Sameeh M.; Maiti, Samarendra N.; Reddy, A. V.N.; Singh, Rajeshwar

doi:10.2174/1568012023354901

Cited by 17 publications

(47 citation statements)

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“…[188] Resistenzen durch Enzyme der Klassen A und C sind heute von besonderer klinischer Bedeutung, doch die anderen Klassen holen auf. Als eine erfolgreiche therapeutische Strategie hat sich die Verabreichung eines b-Lactamase-Inhibitors zusammen mit einem b-Lactam-Antibiotikum erwiesen: [189] Augmentan, die Kombination des b-Lactamase-Inhibitors Clavulansäure (42) mit Amoxycillin (37), ist ein repräsentatives, kommerziell sehr erfolgreiches Beispiel dafür. [190] Clavulansäure (42), gewonnen aus Streptomyces clavuligerus, zählt zu den wenigen natürlichen b-Lactamen, die in unveränderter Form therapeutisch eingesetzt werden.…”

Section: B-lactam-antibiotikaunclassified

Antibakterielle Naturstoffe in der medizinischen Chemie – Exodus oder Renaissance?

et al. 2006

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Zur Entwicklung von Medikamenten müssen die Strukturvorlagen aus der Natur oft durch Semisynthese oder Totalsynthese verbessert werden (chemische Post‐Evolution). Der Weg vom Naturstoff zum Arzneimittel ist mühsam aber lohnenswert. Die grundlegenden Typen der chemischen Naturstoffmodifikation – Dekoration, Substitution und Abbau – werden hier besprochen, und das biologische, chemische und sozioökonomische Umfeld antibakterieller Forschung wird betrachtet. Naturstoffe waren und bleiben die ergiebigste Leitstrukturquelle für vermarktete Antiinfektiva, und obwohl viele lange bekannte Klassen nie grundlegend erforscht worden sind, erlahmen die industrielle wie die akademische Forschung auf diesem Gebiet – die “altmodischen” Naturstoffe scheinen nicht mehr ins Bild der modernen Wirkstoff‐Forschung zu passen, ihre Handhabung ist aufwändig und erfordert oft nichtstandardisierte Prozesse und längere Bearbeitungszeiten. Eine Neubetrachtung von Naturstoffen mit Methoden der modernen Chemie und Biologie (Reversed Genomics) könnte ihre Renaissance in der Arzneimittelforschung einleiten.

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Section: B-lactam-antibiotikaunclassified

Antibakterielle Naturstoffe in der medizinischen Chemie – Exodus oder Renaissance?

et al. 2006

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“…The resultant bromoacetates 9 were converted to desired penems 4a-7a by a reductive elimination procedure. 18 The 6-methyl ester of the seven-membered dihydro [1,4]thiazepine ring system 11a was prepared by reacting penem 4a with sodium methoxide in the presence of anhydrous methanol, as illustrated in Scheme 1B. The seven-membered dihydro- [1,4]thiazepine ring compound 10a was prepared by hydrolysis of 5a in the presence of sodium hydroxide, at room temperature for 1 h (Scheme 1B).…”

Section: Chemistrymentioning

confidence: 99%

“…1 The inhibitor selectively reacts quickly to inactivate the -lactamase, leaving the -lactam antibiotic free to perform its antibacterial function.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Inactivation of β-Lactamases by Novel 6-Methylidene Penems Elucidated Using Electrospray Ionization Mass Spectrometry

Tabei¹,

Feng²,

Venkatesan³

et al. 2004

J. Med. Chem.

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The reactions of 6-methylidene penems 4-7 with beta-lactamases (TEM-1, SHV-1, Amp-C) were characterized by electrospray ionization mass spectrometry (ESI-MS). The kinetics of the reactions were monitored, demonstrating that only one penem molecule reacts to form an acyl-enzyme complex. For penem 5, the ESI-MS/MS spectrum of the hydrolysis product produced in the reaction was identical to the spectrum generated from a synthesized dihydro[1,4]thiazepine 10, confirming the rearrangement of the penem ring system to a seven-membered dihydro[1,4]thiazepine structure. Gas-phase ESI-MS/MS fragmentation data were rationalized due to tautomerization between imine and enamine substructures. ESI-MS/MS analysis of the T-6 trypsin-digested fragments of TEM-1 and SHV-1 demonstrated that the penems were only attached to Ser-70 of these class A beta-lactamases and that the penem ring structures were rearranged to seven-membered dihydro[1,4]thiazepines.

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“…In order to overcome this resistance, several β-lactamase inhibitor/β-lactam antibiotic combinations are currently being used clinically [3] . However, single point mutations within these β-lactamases have made them relatively resistant to inactivation [4,5] . According to Ambler's classification, β-lactamases can be divided into four classes(A to D) based on amino acid sequence homology.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and biological evaluation of sulfenimine cephalosporin analogues as β-lactamase inhibitors

Zhang

Ding

Shi

et al. 2015

Chem. Res. Chin. Univ.

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A series of sulfenimine cephalosporin derivatives(6a-6t) was designed, synthesized and evaluated for their inhibitory activity against class A β-lactamase(TEM-1) derived from E. coli, and class C β-lactamase (cephalosporinase) derived from wild Bacillus subtilis in cell-free systems. Most of the tested compounds showed enhanced inhibitory activity against class C β-lactamase(cephalosporinase) compared with tazobactam. The most promising compounds 6c and 6o in combination with cefradine(IC 50 =1.80 and 1.59 μmol/L, respectively) were further investigated against a series of clinical isolated β-lactamase-producing bacterial strains. The results reveal that compounds 6c and 6o in combination with cefradine show two to four times more activity than cefradine alone against methicillin-sensitive Staphylococcus aureus(MSSA) and Klebsiella pneumoniae. The data suggest that the sulfenimine moiety may be beneficial to the activity and selectivity of inhibitors.

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β-Lactamases and their Inhibitors: An Update

Cited by 17 publications

References 0 publications

Antibakterielle Naturstoffe in der medizinischen Chemie – Exodus oder Renaissance?

Antibakterielle Naturstoffe in der medizinischen Chemie – Exodus oder Renaissance?

Mechanism of Inactivation of β-Lactamases by Novel 6-Methylidene Penems Elucidated Using Electrospray Ionization Mass Spectrometry

Design, synthesis and biological evaluation of sulfenimine cephalosporin analogues as β-lactamase inhibitors

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