Malacidin A
Identification
- Name
- Malacidin A
- Accession Number
- DB14051
- Description
Malacidin A, along with Malacidin B, 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 A appears to act via its own distinct mechanism.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Malacidin A (DB14051)
- Weight
- Average: 1249.384
Monoisotopic: 1248.623783282 - Chemical Formula
- C56H88N12O20
- Synonyms
- Not Available
Pharmacology
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Malacidin A is being investigated for its antibiotic action and has potential for use as an antibacterial agent in the future 1.
- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
Malacidin A 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 A has exhibited broad spectrum activity against Gram-positive bacteria including several multi-drug resistant pathogens.
- Mechanism of action
Malacidin A 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 A 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 A 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 A 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 A retains its activity against Vancomycin-resistant pathogens. Unlike other antibiotic agents, Malacidin A also retains its activity in the presence of pulmonary surfactants.
Target Actions Organism ANAM/NAG peptide subunits of peptidoglycan ligandGram 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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Malacidin A 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAcenocoumarol The risk or severity of bleeding can be increased when Malacidin A is combined with Acenocoumarol. BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Malacidin A. Dicoumarol The risk or severity of bleeding can be increased when Malacidin A is combined with Dicoumarol. Fluindione The risk or severity of bleeding can be increased when Malacidin A is combined with Fluindione. Lactulose The therapeutic efficacy of Lactulose can be decreased when used in combination with Malacidin A. Phenindione The risk or severity of bleeding can be increased when Malacidin A is combined with Phenindione. Phenprocoumon The risk or severity of bleeding can be increased when Malacidin A is combined with Phenprocoumon. Picosulfuric acid The therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Malacidin A. Typhoid vaccine The therapeutic efficacy of Typhoid vaccine can be decreased when used in combination with Malacidin A. Vibrio cholerae CVD 103-HgR strain live antigen The therapeutic efficacy of Vibrio cholerae CVD 103-HgR strain live antigen can be decreased when used in combination with Malacidin A. 
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- Not Available
Categories
- Drug Categories
- Classification
- Not classified
Chemical Identifiers
- UNII
- Not Available
- CAS number
- Not Available
- InChI Key
- USNOUEMKNKRWQT-ORRWAHHJSA-N
- InChI
- InChI=1S/C56H88N12O20/c1-25(2)17-13-11-12-14-19-35(69)62-40(29(8)54(83)84)50(79)66-42-31(10)59-47(76)34-21-28(7)24-68(34)53(82)39(27(5)6)65-49(78)41(30(9)55(85)86)63-36(70)23-58-45(74)33(22-37(71)72)61-52(81)43(44(73)56(87)88)67-46(75)32(18-15-16-20-57)60-48(77)38(26(3)4)64-51(42)80/h11-12,14,19,25-34,38-44,73H,13,15-18,20-24,57H2,1-10H3,(H,58,74)(H,59,76)(H,60,77)(H,61,81)(H,62,69)(H,63,70)(H,64,80)(H,65,78)(H,66,79)(H,67,75)(H,71,72)(H,83,84)(H,85,86)(H,87,88)/b12-11-,19-14+/t28-,29?,30?,31?,32+,33+,34+,38-,39+,40+,41-,42+,43+,44?/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-methylnona-2,4-dienamido]propanoic acid
- SMILES
- CC(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
- 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]
- External Links
Clinical Trials
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
Property Value Source Water Solubility 0.0197 mg/mL ALOGPS logP 0.39 ALOGPS logP -6 ChemAxon logS -4.8 ALOGPS pKa (Strongest Acidic) 2.8 ChemAxon pKa (Strongest Basic) 10.18 ChemAxon Physiological Charge -3 ChemAxon Hydrogen Acceptor Count 21 ChemAxon Hydrogen Donor Count 16 ChemAxon Polar Surface Area 506.76 Å2 ChemAxon Rotatable Bond Count 22 ChemAxon Refractivity 306.63 m3·mol-1 ChemAxon Polarizability 127.11 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets
References
- 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 15:46 / Updated on June 12, 2020 16:53