Malacidin B

Identification

Name
Malacidin B
Accession Number
DB14052
Description

Malacidin B, along with Malacidin A, is a member of a class of chemicals made by bacteria found in soil that can kill Gram-positive bacteria 1. Malacidins are 10-member macrocycle lipopeptides discovered via gene sequencing and bioinformatic analysis. While structurally similar to other macrocycle drugs like Daptomycin and Friulimicin B, Malacidin B appears to act via its own distinct mechanism.

Type
Small Molecule
Groups
Experimental
Structure
Thumb
Weight
Average: 1263.411
Monoisotopic: 1262.639433346
Chemical Formula
C57H90N12O20
Synonyms
Not Available

Pharmacology

Indication

Malacidin B is being investigated for its antibiotic action and has potential for use as an antibacterial agent in the future 1.

Contraindications & Blackbox Warnings
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Pharmacodynamics

Malacidin B disrupts bacterial cell wall synthesis likely leading to cell death in Gram-positive bacteria 1. This bactericidal effect reduces the number of live bacteria present during infection. Malacidin B has exhibited broad spectrum activity against Gram-positive bacteria including several multi-drug resistant pathogens.

Mechanism of action

Malacidin B appears to bind Lipid II via a calcium dependent mechanism despite the absence of the typical Asp-X-Asp-Gly motif associate with calcium binding. The structure of Malacidin B includes a 3-hydroxy-aspartate residue while the "X" variable spacer residue is absent. It is unknown how these unique structural features may impact the drug's mechanism of action. The binding of Malacidin B to Lipid II prevents the incorporation of the subunit into the cell wall, disrupting synthesis and likely resulting in death of the bacterial cell. Malacidin B does not appear to form pores nor does it seem to integrate into the cell wall. While this mechanism is similar to that of Vancomycin, Malacidin B retains its activity against Vancomycin-resistant pathogens. Unlike other antibiotic agents, Malacidin B also retains its activity in the presence of pulmonary surfactants.

TargetActionsOrganism
ANAM/NAG peptide subunits of peptidoglycan
ligand
Gram positive bacteria
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life
Not Available
Clearance
Not Available
Adverse Effects
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Toxicity

Malacidin B has no observed toxicity or haemolytic effect on mammalian cells at concentrations of up to 100-250 μg/mL, over 100 times the MIC for affected pathogens 1.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcenocoumarolThe risk or severity of bleeding can be increased when Malacidin B is combined with Acenocoumarol.
DicoumarolThe risk or severity of bleeding can be increased when Malacidin B is combined with Dicoumarol.
FluindioneThe risk or severity of bleeding can be increased when Malacidin B is combined with Fluindione.
LactuloseThe therapeutic efficacy of Lactulose can be decreased when used in combination with Malacidin B.
PhenindioneThe risk or severity of bleeding can be increased when Malacidin B is combined with Phenindione.
PhenprocoumonThe risk or severity of bleeding can be increased when Malacidin B is combined with Phenprocoumon.
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Malacidin B.
Typhoid vaccineThe therapeutic efficacy of Typhoid vaccine can be decreased when used in combination with Malacidin B.
Vibrio cholerae CVD 103-HgR strain live antigenThe therapeutic efficacy of Vibrio cholerae CVD 103-HgR strain live antigen can be decreased when used in combination with Malacidin B.
WarfarinThe risk or severity of bleeding can be increased when Malacidin B is combined with Warfarin.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

Categories

Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
Not Available
CAS number
Not Available
InChI Key
SMTCDPMWINUUKC-AVBBYWJWSA-N
InChI
InChI=1S/C57H90N12O20/c1-11-28(6)18-14-12-13-15-20-36(70)63-41(30(8)55(84)85)51(80)67-43-32(10)60-48(77)35-22-29(7)25-69(35)54(83)40(27(4)5)66-50(79)42(31(9)56(86)87)64-37(71)24-59-46(75)34(23-38(72)73)62-53(82)44(45(74)57(88)89)68-47(76)33(19-16-17-21-58)61-49(78)39(26(2)3)65-52(43)81/h12-13,15,20,26-35,39-45,74H,11,14,16-19,21-25,58H2,1-10H3,(H,59,75)(H,60,77)(H,61,78)(H,62,82)(H,63,70)(H,64,71)(H,65,81)(H,66,79)(H,67,80)(H,68,76)(H,72,73)(H,84,85)(H,86,87)(H,88,89)/b13-12-,20-15+/t28?,29-,30?,31?,32?,33+,34+,35+,39-,40+,41+,42-,43+,44+,45?/m1/s1
IUPAC Name
(3S)-3-{[(4S,7R,10S,13S,16S,22R,25S,29R,30aS)-10-(4-aminobutyl)-13-[carboxy(hydroxy)methyl]-22-(1-carboxyethyl)-16-(carboxymethyl)-3,29-dimethyl-1,5,8,11,14,17,20,23,26-nonaoxo-7,25-bis(propan-2-yl)-triacontahydropyrrolo[2,1-c]1,4,7,10,13,16,19,22,25-nonaazacyclooctacosan-4-yl]carbamoyl}-2-methyl-3-[(2E,4Z)-8-methyldeca-2,4-dienamido]propanoic acid
SMILES
CCC(C)CC\C=C/C=C/C(=O)N[C@@H](C(C)C(O)=O)C(=O)N[C@H]1C(C)NC(=O)[C@@H]2C[C@@H](C)CN2C(=O)[C@@H](NC(=O)[C@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](NC1=O)C(C)C)C(O)C(O)=O)C(C)C(O)=O)C(C)C

References

Synthesis Reference

Hover BM, Kim SH, Katz M, et al. Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens. Nat Microbiol. 2018;3(4):415-422.

General References
  1. Hover BM, Kim SH, Katz M, Charlop-Powers Z, Owen JG, Ternei MA, Maniko J, Estrela AB, Molina H, Park S, Perlin DS, Brady SF: Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens. Nat Microbiol. 2018 Apr;3(4):415-422. doi: 10.1038/s41564-018-0110-1. Epub 2018 Feb 12. [PubMed:29434326]
ChEBI
140174

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0167 mg/mLALOGPS
logP0.59ALOGPS
logP-5.6ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)2.8ChemAxon
pKa (Strongest Basic)10.18ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count21ChemAxon
Hydrogen Donor Count16ChemAxon
Polar Surface Area506.76 Å2ChemAxon
Rotatable Bond Count23ChemAxon
Refractivity311.23 m3·mol-1ChemAxon
Polarizability129.37 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

1. NAM/NAG peptide subunits of peptidoglycan
Kind
Group
Organism
Gram positive bacteria
Pharmacological action
Yes
Actions
Ligand
References
  1. Hover BM, Kim SH, Katz M, Charlop-Powers Z, Owen JG, Ternei MA, Maniko J, Estrela AB, Molina H, Park S, Perlin DS, Brady SF: Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens. Nat Microbiol. 2018 Apr;3(4):415-422. doi: 10.1038/s41564-018-0110-1. Epub 2018 Feb 12. [PubMed:29434326]

Drug created on June 11, 2018 09:49 / Updated on June 12, 2020 10:53

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