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Identification
NameMezlocillin
Accession NumberDB00948  (APRD01113)
TypeSmall Molecule
GroupsApproved
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
Mezlin
Mezlocilina
Mezlocillin
Mezlocilline
Mezlocillinum
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
MezlinNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Mezlocillin sodium monohydrate
ThumbNot applicableDBSALT001339
Categories
UNIIOH2O403D1G
CAS number51481-65-3
WeightAverage: 539.582
Monoisotopic: 539.114454181
Chemical FormulaC21H25N5O8S2
InChI KeyInChIKey=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)[[email protected]]2NC(=O)[[email protected]](NC(=O)N1CCN(C1=O)S(C)(=O)=O)C1=CC=CC=C1)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as penicillins. These are organic compounds containing the penicillin core structure, which is structurally characterized by a penam ring bearing two methyl groups at position 2, and an amide group at position 6 [starting from the sulfur atom at position 1].
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassLactams
Sub ClassBeta lactams
Direct ParentPenicillins
Alternative Parents
Substituents
  • Penicillin
  • N-carbamoyl-alpha-amino acid or derivatives
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid amide
  • Phenylacetamide
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Sulfonylurea
  • Benzenoid
  • Imidazolidinone
  • Monocyclic benzene moiety
  • Thiazolidine
  • Tertiary carboxylic acid amide
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Imidazolidine
  • Urea
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azetidine
  • Azacycle
  • Dialkylthioether
  • Hemithioaminal
  • Thioether
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationUsed to treat serious gram–negative infections of the lungs, urinary tract, and skin.
PharmacodynamicsMezlocillin 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 actionBy 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding16-59%
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 eliminationNot Available
Half life1.3 to 4.4 hours
ClearanceNot Available
ToxicitySymptoms of overdose include rash, fever, chills, and peeling skin.
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Bayer pharmaceuticals corp
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesJ01CA10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcenocoumarolMezlocillin may increase the anticoagulant activities of Acenocoumarol.
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Mezlocillin.
BiotinThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Biotin.
DemeclocyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Demeclocycline.
DoxycyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Doxycycline.
GentamicinThe serum concentration of Gentamicin can be decreased when it is combined with Mezlocillin.
KanamycinThe serum concentration of Kanamycin can be decreased when it is combined with Mezlocillin.
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Mezlocillin.
MinocyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Minocycline.
Mycophenolate mofetilThe serum concentration of the active metabolites of Mycophenolate mofetil can be reduced when Mycophenolate mofetil is used in combination with Mezlocillin resulting in a loss in efficacy.
Mycophenolic acidThe serum concentration of the active metabolites of Mycophenolic acid can be reduced when Mycophenolic acid is used in combination with Mezlocillin resulting in a loss in efficacy.
NeomycinThe serum concentration of Neomycin can be decreased when it is combined with Mezlocillin.
ProbenecidThe serum concentration of Mezlocillin can be increased when it is combined with Probenecid.
StreptomycinThe serum concentration of Streptomycin can be decreased when it is combined with Mezlocillin.
TetracyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Tetracycline.
TobramycinThe serum concentration of Tobramycin can be decreased when it is combined with Mezlocillin.
WarfarinMezlocillin may increase the anticoagulant activities of Warfarin.
Food InteractionsNot Available

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 strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits) (By similarity).
Gene Name:
pbpA
Uniprot ID:
Q8XJ01
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
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
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 ]
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Drug created on June 13, 2005 07:24 / Updated on November 26, 2015 17:26