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Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-M β-Lactamase

Journal Article · · Organometallics
 [1];  [2];  [1];  [2];  [3];  [3];  [4];  [2];  [1]
  1. Univ. of South Florida, Tampa, FL (United States). Morsani College of Medicine
  2. Univ. of Łódź, Tamka (Poland)
  3. National Inst. of Public Health - National Inst. of Hygiene (NIPH-NIH), Warsaw (Poland)
  4. Univ. of Zagreb (Croatia)
+ Show Author Affiliations
We report a series of six novel metallocenyl-7-ADCA (metallocenyl = ferrocenyl or ruthenocenyl; 7-ADCA = 7- aminodesacetoxycephalosporanic acid) conjugates were synthesized and their antibacterial properties evaluated by biochemical and microbiological assays. The ruthenocene derivatives showed a higher level of inhibition of DDcarboxypeptidase 64-575, a penicillin binding protein (PBP), than the ferrocene derivatives and the reference compound penicillin G. Protein X-ray crystallographic analysis revealed a covalent acyl–enzyme complex of a ruthenocenyl compound with CTX-M β-lactamase E166A mutant, corresponding to a similar complex with PBPs responsible for the bactericidal activities of these compounds. Most interestingly, an intact compound was captured at the crystal-packing interface, elucidating for the first time the structure of a metallocenyl β-lactam compound that previously eluded small-molecule crystallography. We propose that protein crystals, even from biologically unrelated molecules, can be utilized to determine structures of small molecules.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
National Institutes of Health (NIH); National Science Centre of Poland (NCN)
OSTI ID:
1463718
Journal Information:
Organometallics, Journal Name: Organometallics Journal Issue: 9 Vol. 36; ISSN 0276-7333
Publisher:
American Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Cited By (8)

Cymantrenyl-Nucleobases: Synthesis, Anticancer, Antitrypanosomal and Antimicrobial Activity Studies journal December 2017
Synthesis, Structural Characterization and Antimicrobial Activity of Cu(II) and Fe(III) Complexes Incorporating Azo-Azomethine Ligand journal April 2018
Synthesis, Characterisation and Antimicrobial Studies of some 2,6‐ bis (1,2,3‐Triazol‐4‐yl)Pyridine Ruthenium(II) “Click” Complexes journal March 2019
Quinoline and ferrocene conjugates: Synthesis, computational study and biological evaluations: Quinoline-ferrocene conjugates journal November 2018
Insight into the Biological Activity of Organometallic Acetylsalicylic Acid (Aspirin) Derivatives journal April 2019
Anticancer and Antibacterial Activity of Transition Metal Complexes journal February 2019
Antimicrobial activity of organometallic isonicotinyl and pyrazinyl ferrocenyl-derived complexes journal January 2017
Organometallic ciprofloxacin conjugates with dual action: synthesis, characterization, and antimicrobial and cytotoxicity studies journal January 2020

Figures / Tables (4)

Scheme 1(p. 2)figure Scheme 1
Table 1(p. 2)table Table 1
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Figure 2(p. 3)figure Figure 2

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Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Antimicrobial agents
Crystal structure
Crystals
Monomers
Peptides and proteins