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Identification
NameMezlocillin
Accession NumberDB00948  (APRD01113)
TypeSmall Molecule
GroupsApproved
DescriptionSemisynthetic 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 KeyYPBATNHYBCGSSN-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
Pharmacology
IndicationUsed to treat serious gram–negative infections of the lungs, urinary tract, and skin.
Structured Indications Not Available
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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Penicillin-binding protein 1AProteinyes
inhibitor
Clostridium perfringens (strain 13 / Type A)Q8XJ01 details
Penicillin-binding protein 3Proteinyes
inhibitor
Streptococcus pneumoniaeQ75Y35 details
Penicillin-binding protein 2Proteinunknown
inhibitor
Escherichia coli (strain K12)P0AD65 details
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
Interactions
Drug Interactions
DrugInteractionDrug group
AcenocoumarolMezlocillin may increase the anticoagulant activities of Acenocoumarol.Approved
AclarubicinThe serum concentration of Aclarubicin can be decreased when it is combined with Mezlocillin.Investigational
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Mezlocillin.Approved, Vet Approved
AmrubicinThe serum concentration of Amrubicin can be decreased when it is combined with Mezlocillin.Approved, Investigational
annamycinThe serum concentration of annamycin can be decreased when it is combined with Mezlocillin.Investigational
ApramycinThe serum concentration of Apramycin can be decreased when it is combined with Mezlocillin.Experimental, Vet Approved
ArbekacinThe serum concentration of Arbekacin can be decreased when it is combined with Mezlocillin.Approved
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Mezlocillin.Investigational
ChlortetracyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Chlortetracycline.Approved, Vet Approved
DaunorubicinThe serum concentration of Daunorubicin can be decreased when it is combined with Mezlocillin.Approved
DemeclocyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Demeclocycline.Approved
DicoumarolMezlocillin may increase the anticoagulant activities of Dicoumarol.Approved
DihydrostreptomycinThe serum concentration of Dihydrostreptomycin can be decreased when it is combined with Mezlocillin.Vet Approved
DoxorubicinThe serum concentration of Doxorubicin can be decreased when it is combined with Mezlocillin.Approved, Investigational
DoxycyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Doxycycline.Approved, Investigational, Vet Approved
EpirubicinThe serum concentration of Epirubicin can be decreased when it is combined with Mezlocillin.Approved
Ethyl biscoumacetateMezlocillin may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneMezlocillin may increase the anticoagulant activities of Fluindione.Investigational
FramycetinThe serum concentration of Framycetin can be decreased when it is combined with Mezlocillin.Approved
GeneticinThe serum concentration of Geneticin can be decreased when it is combined with Mezlocillin.Experimental
GentamicinThe serum concentration of Gentamicin can be decreased when it is combined with Mezlocillin.Approved, Vet Approved
GENTAMICIN C1AThe serum concentration of GENTAMICIN C1A can be decreased when it is combined with Mezlocillin.Experimental
Hygromycin BThe serum concentration of Hygromycin B can be decreased when it is combined with Mezlocillin.Vet Approved
IdarubicinThe serum concentration of Idarubicin can be decreased when it is combined with Mezlocillin.Approved
INNO-206The serum concentration of INNO-206 can be decreased when it is combined with Mezlocillin.Investigational
KanamycinThe serum concentration of Kanamycin can be decreased when it is combined with Mezlocillin.Approved, Vet Approved
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Mezlocillin.Approved
MetrizamideThe serum concentration of Metrizamide can be decreased when it is combined with Mezlocillin.Approved
MinocyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Minocycline.Approved, Investigational
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.Approved
NeamineThe serum concentration of Neamine can be decreased when it is combined with Mezlocillin.Experimental
NeomycinThe serum concentration of Neomycin can be decreased when it is combined with Mezlocillin.Approved, Vet Approved
NetilmicinThe serum concentration of Netilmicin can be decreased when it is combined with Mezlocillin.Approved
OxytetracyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Oxytetracycline.Approved, Vet Approved
ParomomycinThe serum concentration of Paromomycin can be decreased when it is combined with Mezlocillin.Approved, Investigational
PhenindioneMezlocillin may increase the anticoagulant activities of Phenindione.Approved
PhenprocoumonMezlocillin may increase the anticoagulant activities of Phenprocoumon.Approved
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Mezlocillin.Approved
PirarubicinThe serum concentration of Pirarubicin can be decreased when it is combined with Mezlocillin.Investigational
PlicamycinThe serum concentration of Plicamycin can be decreased when it is combined with Mezlocillin.Approved, Withdrawn
ProbenecidThe serum concentration of Mezlocillin can be increased when it is combined with Probenecid.Approved
PuromycinThe serum concentration of Puromycin can be decreased when it is combined with Mezlocillin.Experimental
RibostamycinThe serum concentration of Ribostamycin can be decreased when it is combined with Mezlocillin.Approved
SisomicinThe serum concentration of Sisomicin can be decreased when it is combined with Mezlocillin.Investigational
SP1049CThe serum concentration of SP1049C can be decreased when it is combined with Mezlocillin.Investigational
SpectinomycinThe serum concentration of Spectinomycin can be decreased when it is combined with Mezlocillin.Approved, Vet Approved
StreptomycinThe serum concentration of Streptomycin can be decreased when it is combined with Mezlocillin.Approved, Vet Approved
StreptozocinThe serum concentration of Streptozocin can be decreased when it is combined with Mezlocillin.Approved
TetracyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Tetracycline.Approved, Vet Approved
TobramycinThe serum concentration of Tobramycin can be decreased when it is combined with Mezlocillin.Approved, Investigational
ValrubicinThe serum concentration of Valrubicin can be decreased when it is combined with Mezlocillin.Approved
WarfarinMezlocillin may increase the anticoagulant activities of Warfarin.Approved
ZorubicinThe serum concentration of Zorubicin can be decreased when it is combined with Mezlocillin.Experimental
Food InteractionsNot 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
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
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
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

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 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23