Identification

Name
Mezlocillin
Accession Number
DB00948  (APRD01113)
Type
Small Molecule
Groups
Approved, Investigational
Description

Semisynthetic ampicillin-derived acylureido penicillin. It has been proposed for infections with certain anaerobes and may be useful in inner ear, bile, and CNS infections. [PubChem]

Structure
Thumb
Synonyms
  • (2S,5R,6R)-3,3-Dimethyl-6-{[(2R)-2-({[3-(methylsulfonyl)-2-oxoimidazolidin-1-yl]carbonyl}amino)-2-phenylacetyl]amino}-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
  • 6beta-{(2R)-2-[3-(methanesulfonyl)-2-oxoimidazolidine-1-carboxamido]-2-phenylacetamido}penicillanic acid
  • Mezlocilina
  • Mezlocillin
  • Mezlocilline
  • Mezlocillinum
External IDs
BAY-F-1353
Product Ingredients
IngredientUNIICASInChI Key
Mezlocillin sodiumRX227TP94U42057-22-7GTGQRSIMEUWHPA-ZBJAFUORSA-M
Mezlocillin sodium monohydrate3CWW8B590480495-46-1CZXDIDROKIDGNE-SYNJJEHYSA-M
International/Other Brands
Mezlin
Categories
UNII
OH2O403D1G
CAS number
51481-65-3
Weight
Average: 539.582
Monoisotopic: 539.114454181
Chemical Formula
C21H25N5O8S2
InChI Key
YPBATNHYBCGSSN-VWPFQQQWSA-N
InChI
InChI=1S/C21H25N5O8S2/c1-21(2)14(18(29)30)26-16(28)13(17(26)35-21)22-15(27)12(11-7-5-4-6-8-11)23-19(31)24-9-10-25(20(24)32)36(3,33)34/h4-8,12-14,17H,9-10H2,1-3H3,(H,22,27)(H,23,31)(H,29,30)/t12-,13-,14+,17-/m1/s1
IUPAC Name
(2S,5R,6R)-6-[(2R)-2-[(3-methanesulfonyl-2-oxoimidazolidine-1-carbonyl)amino]-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
SMILES
[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](NC(=O)N1CCN(C1=O)S(C)(=O)=O)C1=CC=CC=C1)C(O)=O

Pharmacology

Indication

Used to treat serious gram–negative infections of the lungs, urinary tract, and skin.

Pharmacodynamics

Mezlocillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Mezlocillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of mezlocillin results from the inhibition of cell wall synthesis and is mediated through mezlocillin binding to penicillin binding proteins (PBPs). Mezlocillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. Mezlocillin can be used to treat susceptible strains of H. influenzae, Klebsiella species, Pseudomonas species, Proteus mirabilis, E. coli, Enterobacter species, Streptococcus faecelis, Peptococcus species, Peptostreptococcus species, Bacteriodes species (including B. fragilis), Morganella morganii, Serratia species, N. gonorrhoeae, P. vulgaris, and Providencia rettgeri. This drug is discontinued in the U.S.

Mechanism of action

By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, mezlocillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that mezlocillin interferes with an autolysin inhibitor.

TargetActionsOrganism
APenicillin-binding protein 1A
inhibitor
Clostridium perfringens (strain 13 / Type A)
APenicillin-binding protein 3
inhibitor
Streptococcus pneumoniae
UPenicillin-binding protein 2
inhibitor
Escherichia coli (strain K12)
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

16-59%

Metabolism

Unlike many other penicillins, mezlocillin is either extensively metabolized or is subject to biliary excretion, as only about 50% of the dose was accounted for in normal urine.

Route of elimination
Not Available
Half life

1.3 to 4.4 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include rash, fever, chills, and peeling skin.

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcenocoumarolMezlocillin may increase the anticoagulant activities of Acenocoumarol.
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Mezlocillin.
ApramycinThe serum concentration of Apramycin can be decreased when it is combined with Mezlocillin.
ArbekacinThe serum concentration of Arbekacin can be decreased when it is combined with Mezlocillin.
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Mezlocillin.
BekanamycinThe serum concentration of Bekanamycin can be decreased when it is combined with Mezlocillin.
CapreomycinThe serum concentration of Capreomycin can be decreased when it is combined with Mezlocillin.
ChlortetracyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Chlortetracycline.
ClorindioneMezlocillin may increase the anticoagulant activities of Clorindione.
DemeclocyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Demeclocycline.
Food Interactions
Not Available

References

General References
  1. Kristof RA, Clusmann H, Koehler W, Fink KB, Schramm J: Treatment of accidental high dose intraventricular mezlocillin application by cerebrospinal fluid exchange. J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):379-81. [PubMed:9527154]
  2. McCormick PA, Greenslade L, Kibbler CC, Chin JK, Burroughs AK, McIntyre N: A prospective randomized trial of ceftazidime versus netilmicin plus mezlocillin in the empirical therapy of presumed sepsis in cirrhotic patients. Hepatology. 1997 Apr;25(4):833-6. [PubMed:9096584]
  3. Rohde B, Werner U, Hickstein H, Ehmcke H, Drewelow B: Pharmacokinetics of mezlocillin and sulbactam under continuous veno-venous hemodialysis (CVVHD) in intensive care patients with acute renal failure. Eur J Clin Pharmacol. 1997;53(2):111-5. [PubMed:9403281]
External Links
Human Metabolome Database
HMDB0015083
KEGG Drug
D05021
KEGG Compound
C07221
PubChem Compound
656511
PubChem Substance
46506692
ChemSpider
570894
ChEBI
6919
ChEMBL
CHEMBL1731
Therapeutic Targets Database
DAP001180
PharmGKB
PA164750540
Wikipedia
Mezlocillin
ATC Codes
J01CR50 — Combinations of penicillinsJ01CA10 — Mezlocillin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1

Pharmacoeconomics

Manufacturers
  • Bayer pharmaceuticals corp
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP0Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.471 mg/mLALOGPS
logP0.21ALOGPS
logP-0.84ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)3.49ChemAxon
pKa (Strongest Basic)-5.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area173.5 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity124.88 m3·mol-1ChemAxon
Polarizability51.5 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8903
Blood Brain Barrier-0.9802
Caco-2 permeable-0.6285
P-glycoprotein substrateSubstrate0.7696
P-glycoprotein inhibitor INon-inhibitor0.817
P-glycoprotein inhibitor IINon-inhibitor0.9892
Renal organic cation transporterNon-inhibitor0.8761
CYP450 2C9 substrateNon-substrate0.5979
CYP450 2D6 substrateNon-substrate0.7973
CYP450 3A4 substrateNon-substrate0.5132
CYP450 1A2 substrateNon-inhibitor0.8033
CYP450 2C9 inhibitorNon-inhibitor0.7397
CYP450 2D6 inhibitorNon-inhibitor0.8934
CYP450 2C19 inhibitorNon-inhibitor0.7272
CYP450 3A4 inhibitorNon-inhibitor0.7478
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9747
Ames testNon AMES toxic0.6484
CarcinogenicityNon-carcinogens0.8275
BiodegradationReady biodegradable0.8269
Rat acute toxicity2.5003 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9907
hERG inhibition (predictor II)Non-inhibitor0.7489
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as peptides. These are compounds containing an amide derived from two or more amino carboxylic acid molecules (the same or different) by formation of a covalent bond from the carbonyl carbon of one to the nitrogen atom of another.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Peptides
Alternative Parents
Penicillins / N-carbamoyl-alpha amino acids and derivatives / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Phenylacetamides / Sulfonylureas / Imidazolidinones / Thiazolidines / Tertiary carboxylic acid amides / Sulfonyls
show 13 more
Substituents
Alpha peptide / Penicillin / N-acyl-alpha amino acid or derivatives / N-carbamoyl-alpha-amino acid or derivatives / Alpha-amino acid amide / N-substituted-alpha-amino acid / Alpha-amino acid or derivatives / Phenylacetamide / Penam / Sulfonylurea
show 33 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
penicillin (CHEBI:6919)

Targets

Kind
Protein
Organism
Clostridium perfringens (strain 13 / Type A)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transferase activity, transferring glycosyl groups
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
pbpA
Uniprot ID
Q8XJ01
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
75176.35 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Lei Y, Li JT: [Affinity of penicillin-binding proteins of Escherichia coli K-12 for furbenicillin and other beta-lactam antibiotics]. Zhongguo Yao Li Xue Bao. 1989 Mar;10(2):177-80. [PubMed:2683579]
Kind
Protein
Organism
Streptococcus pneumoniae
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Not Available
Gene Name
pbp3
Uniprot ID
Q75Y35
Uniprot Name
Penicillin-binding protein 3
Molecular Weight
45209.84 Da
References
  1. Lei Y, Li JT: [Affinity of penicillin-binding proteins of Escherichia coli K-12 for furbenicillin and other beta-lactam antibiotics]. Zhongguo Yao Li Xue Bao. 1989 Mar;10(2):177-80. [PubMed:2683579]
  2. Drugeon HB, Caillon J, Moinard D, Juvin ME, Pirault JL: [Bactericidal effect of piperacillin alone and combined]. Presse Med. 1986 Dec 20;15(46):2297-302. [PubMed:2949271]
  3. McCloskey RV, LeFrock JL, Smith BR, Aronoff GR: Microbiology, pharmacology, and clinical use of mezlocillin sodium. Pharmacotherapy. 1982 Nov-Dec;2(6):300-12. [PubMed:6220263]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Cell wall formation; PBP-2 is responsible for the determination of the rod shape of the cell. It synthesizes cross-linked peptidoglycan from lipid intermediates.
Gene Name
mrdA
Uniprot ID
P0AD65
Uniprot Name
Penicillin-binding protein 2
Molecular Weight
70856.1 Da
References
  1. Lei Y, Li JT: [Affinity of penicillin-binding proteins of Escherichia coli K-12 for furbenicillin and other beta-lactam antibiotics]. Zhongguo Yao Li Xue Bao. 1989 Mar;10(2):177-80. [PubMed:2683579]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:46