Azetidinone-isothiazolidinones: Stereoselective synthesis and antibacterial evaluation of new monocyclic beta-lactams

Cerić, Helena; Šindler‐Kulyk, Marija; Kovačević, Miće; Perić, Mihaela; Zivkovic, Andreja

doi:10.1016/j.bmc.2010.03.045

Cited by 28 publications

(13 citation statements)

References 21 publications

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“…The following Gram-positive and Gram-negative bacterial species were included: Streptococcus pyogenes (10), Streptococcus pneumoniae (10), Enterococcus faecalis (10), methicillin-resistant Staphylococcus aureus (MRSA) (13), methicillin-susceptible S. aureus (MSSA) (13), Staphylococcus epidermidis (10), Haemophilus influenzae (10), Escherichia coli (10), Proteus mirabilis (10), Serratia marcescens (10), and Klebsiella pneumoniae (10). In addition, a total of 20 MSSA and MRSA strains had been recently isolated from pediatric patients with cystic fibrosis at the Department of Pediatrics, CF Center, Foundation IRCCS CA' GRANDA Ospedale Maggiore Policlinico, University of Milan (Italy); these were further tested for their susceptibility toward the most active compounds.…”

Section: Bacterial Strainsmentioning

confidence: 99%

“…[10] We have actively contributed to this field with the design and synthesis of monocyclic b-lactams, having discovered 4-alkylideneazetidinones as interesting scaffolds for antibiotics against resistant bacteria, [11] and as effective enzyme inhibitors. [12] In these derivatives the carboncarbon double bond directly linked to the azetidinone ring confers an increased aptitude toward ring-opening reactions.…”

Section: Introductionmentioning

confidence: 99%

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Antibacterial Agents and Cystic Fibrosis: Synthesis and Antimicrobial Evaluation of a Series of N‐Thiomethylazetidinones

et al. 2011

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The increasing emergence of multidrug-resistant microorganisms is one of the greatest challenges in the clinical management of infectious disease. New antimicrobial agents are therefore urgently required, particularly in the treatment of chronic and recurrent infections often associated with antibiotic-resistant pathogens, as in the case of cystic fibrosis (CF) patients. This study reports the antibacterial activity of a series of monocyclic β-lactams with an alkylidenecarboxyl chain or electron-withdrawing groups such as 4-OAc, 4-SAc, and 4-SO(2)Ph at the C4 position of the ring. N-Unsubstituted and N-thiomethyl derivatives were compared. A total of 33 azetidinones were tested for their activity against Gram-positive and Gram-negative bacterial clinical isolates. The combination of an N-thiomethyl group and a benzyl ester on the 4-alkylidene side chain were found to increase the potency against Gram-positive bacteria. The N-thiomethyl group clearly elevated the activity of 4-acetoxyazetidinones relative to the corresponding NH derivatives. The most active compounds showed minimum inhibitory concentration (MIC) values of 4 and 8 mg L(-1) against methicillin-resistant Staphylococcus aureus isolated from pediatric patients with CF.

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Section: Bacterial Strainsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antibacterial Agents and Cystic Fibrosis: Synthesis and Antimicrobial Evaluation of a Series of N‐Thiomethylazetidinones

et al. 2011

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“…4-Chloro azetidinones are not evaluated by biological tests per se because they are generally used as intermediates in the synthesis of other bicyclic beta-lactams. However, a paper on the biological activity of some 4-chloroazetidinones recently appeared [36]. Those compounds present an azetidinone-isothiazolidinone structure.…”

Section: -Chloro-azetidinonesmentioning

confidence: 99%

Monocyclic β-Lactams: New Structures for New Biological Activities

Galletti

Giacomini

2011

CMC

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The azetidinone core-structure offers a unique approach to the design and synthesis of new derivatives with unique biological properties. During the last two decades researches convincingly demonstrated that the prospect of structural modifications of monocyclic β-lactams with specific substituents is an effective procedure for the detection and improvement of important pharmacological effects different from antibacterial activity. As a matter of fact, new β-lactam compounds demonstrated biological activity as inhibitors of a wide range of enzymes. This review reports the latest developments on monocyclic β-lactam compounds activity as anticancer, antitubercular, HFAAH inhibitors, HDAC inhibitors, anti-inflammatory drugs (tryptase inhibitors), Cathepsin K inhibitors, and vasopressin inhibitors. We attempted to highlight the intertwined relationships between structural features and biological activities, by analysing groups anchored on the three positions of the azetidinone ring as sources of molecular diversity.

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“…So, the synthesis of monocyclic β-lactam derivatives that could be more effective than the existing compounds has become an important subject of medicinal interest. 7,8 Accordingly, here I report the design and synthesis of two new monocyclic β-lactams that contain penicillin-similar moieties.…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of New 4-Alkylthio Monocyclic β-Lactams

Lee

2013

Bulletin of the Korean Chemical Society

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New types of monocyclic β-lactams constitute an important class of compounds due to their unique structures and natures. Here, the design and synthesis of new 4-alkylthio monocyclic β-lactams 2a and 3a are reported. Significantly, compounds 2a and 3a, while keeping a monocyclic system, were designed to contain all of the substructures provided by the cleavage of C(2)-C(3) bond in penicillins. Efficient synthetic pathways for compounds 2a and 3a were established based on two different strategies. Compound 2a was synthesized from raw materials, using 4-acetoxyazetidin-2-one as a key intermediate, through a ten-step synthetic sequence in 3% overall yield. Compound 3a was synthesized from potassium salt of penicillin G (17), using the degraded product 20 as a key intermediate, through a six-step synthetic sequence in 11% overall yield. 4-Alkylthioazetidin-2-one derivatives, introduced in this study, could serve as valuable intermediates for the development of new monocyclic β-lactams.

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Azetidinone-isothiazolidinones: Stereoselective synthesis and antibacterial evaluation of new monocyclic beta-lactams

Cited by 28 publications

References 21 publications

Antibacterial Agents and Cystic Fibrosis: Synthesis and Antimicrobial Evaluation of a Series of N‐Thiomethylazetidinones

Antibacterial Agents and Cystic Fibrosis: Synthesis and Antimicrobial Evaluation of a Series of N‐Thiomethylazetidinones

Monocyclic β-Lactams: New Structures for New Biological Activities

Design and Synthesis of New 4-Alkylthio Monocyclic β-Lactams

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Azetidinone-isothiazolidinones: Stereoselective synthesis and antibacterial evaluation of new monocyclic beta-lactams

Cited by 28 publications

References 21 publications

Antibacterial Agents and Cystic Fibrosis: Synthesis and Antimicrobial Evaluation of a Series of N‐Thiomethylazetidinones

Antibacterial Agents and Cystic Fibrosis: Synthesis and Antimicrobial Evaluation of a Series of N‐Thiomethylazetidinones

Monocyclic &#946;-Lactams: New Structures for New Biological Activities

Design and Synthesis of New 4-Alkylthio Monocyclic β-Lactams

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Monocyclic β-Lactams: New Structures for New Biological Activities