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.

Structure

Similar Structures

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
6β-{(2R)-2-[3-(methanesulfonyl)-2-oxoimidazolidine-1-carboxamido]-2-phenylacetamido}penicillanic acid
Mezlocilina
Mezlocillin
Mezlocilline
Mezlocillinum

External IDs

BAY-F-1353

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Mezlocillin sodium	RX227TP94U	42057-22-7	GTGQRSIMEUWHPA-ZBJAFUORSA-M
Mezlocillin sodium monohydrate	3CWW8B5904	80495-46-1	CZXDIDROKIDGNE-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.

Target	Actions	Organism
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

Drug	Interaction
(R)-warfarin	Mezlocillin may increase the anticoagulant activities of (R)-warfarin.
(S)-Warfarin	Mezlocillin may increase the anticoagulant activities of (S)-Warfarin.
4-hydroxycoumarin	Mezlocillin may increase the anticoagulant activities of 4-hydroxycoumarin.
Acemetacin	Acemetacin may decrease the excretion rate of Mezlocillin which could result in a higher serum level.
Acenocoumarol	Mezlocillin may increase the anticoagulant activities of Acenocoumarol.
Adenovirus type 7 vaccine live	The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Mezlocillin.
Alcuronium	The therapeutic efficacy of Alcuronium can be increased when used in combination with Mezlocillin.
Amikacin	The serum concentration of Amikacin can be decreased when it is combined with Mezlocillin.
Anthrax immune globulin human	The therapeutic efficacy of Anthrax immune globulin human can be decreased when used in combination with Mezlocillin.
Anthrax vaccine	The therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Mezlocillin.

Food Interactions

Not Available

References

General References

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]
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]
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 penicillins

J01CA10 — Mezlocillin

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
0	Recruiting	Treatment	Osteomyelitis	1

Pharmacoeconomics

Manufacturers

Bayer pharmaceuticals corp

Packagers

Not Available

Dosage forms

Not Available

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
logP	0	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.471 mg/mL	ALOGPS
logP	0.21	ALOGPS
logP	-0.84	ChemAxon
logS	-3.1	ALOGPS
pKa (Strongest Acidic)	3.49	ChemAxon
pKa (Strongest Basic)	-5.9	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	8	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	173.5 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	124.88 m³·mol^-1	ChemAxon
Polarizability	51.5 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	-	0.8903
Blood Brain Barrier	-	0.9802
Caco-2 permeable	-	0.6285
P-glycoprotein substrate	Substrate	0.7696
P-glycoprotein inhibitor I	Non-inhibitor	0.817
P-glycoprotein inhibitor II	Non-inhibitor	0.9892
Renal organic cation transporter	Non-inhibitor	0.8761
CYP450 2C9 substrate	Non-substrate	0.5979
CYP450 2D6 substrate	Non-substrate	0.7973
CYP450 3A4 substrate	Non-substrate	0.5132
CYP450 1A2 substrate	Non-inhibitor	0.8033
CYP450 2C9 inhibitor	Non-inhibitor	0.7397
CYP450 2D6 inhibitor	Non-inhibitor	0.8934
CYP450 2C19 inhibitor	Non-inhibitor	0.7272
CYP450 3A4 inhibitor	Non-inhibitor	0.7478
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9747
Ames test	Non AMES toxic	0.6484
Carcinogenicity	Non-carcinogens	0.8275
Biodegradation	Ready biodegradable	0.8269
Rat acute toxicity	2.5003 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9907
hERG inhibition (predictor II)	Non-inhibitor	0.7489

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not 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

Details1. Penicillin-binding protein 1A

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

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]
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]
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]

Details2. Penicillin-binding protein 3

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

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]
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]
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]

Details3. Penicillin-binding protein 2

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

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 April 23, 2019 11:17

Mezlocillin

Identification

Structure for Mezlocillin (DB00948)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

References