Abaucin

Last updated
Abaucin
Abaucin.svg
Identifiers
  • 1'-[2-[4-(trifluoromethyl)phenyl]ethyl]spiro[1H-3,1-benzoxazine-4,4'-piperidine]-2-one
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
ChEBI
ChEMBL
Chemical and physical data
Formula C21H21F3N2O2
Molar mass 390.406 g·mol−1
3D model (JSmol)
  • C1CN(CCC12C3=CC=CC=C3NC(=O)O2)CCC4=CC=C(C=C4)C(F)(F)F
  • InChI=1S/C21H21F3N2O2/c22-21(23,24)16-7-5-15(6-8-16)9-12-26-13-10-20(11-14-26)17-3-1-2-4-18(17)25-19(27)28-20/h1-8H,9-14H2,(H,25,27)
  • Key:HIDWEYPGMLIQSN-UHFFFAOYSA-N

Abaucin (RS-102895, MLJS-21001) is a compound which has been reported to show useful activity as a narrow-spectrum antibiotic. [1] There is evidence that it is effective against Acinetobacter baumannii , which is one of the three superbugs identified by the World Health Organization as a "critical threat" to humanity. Notably, abaucin was developed with assistance from artificial intelligence by a team led by the MIT Jameel Clinic's faculty lead for life sciences, James J. Collins, and McMaster's Jonathan Stokes. [2] [3] [4] Its mode of action involves inhibiting lipoprotein transport. The compound had previously been reported as an antagonist of the chemokine receptor CCR2, but its antibiotic activity was not discovered during earlier research. [5] [6] [7] [8] [9]

A New York Times opinion piece by Peter Coy for Thanksgiving listed abaucin among scientific discoveries to be thankful for in 2023. [10]

See also

Related Research Articles

<i>Acinetobacter</i> Genus of bacteria

Acinetobacter is a genus of Gram-negative bacteria belonging to the wider class of Gammaproteobacteria. Acinetobacter species are oxidase-negative, exhibit twitching motility, and occur in pairs under magnification.

<span class="mw-page-title-main">Colistin</span> Antibiotic

Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram-negative infections including pneumonia. These may involve bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae, or Acinetobacter. It comes in two forms: colistimethate sodium can be injected into a vein, injected into a muscle, or inhaled, and colistin sulfate is mainly applied to the skin or taken by mouth. Colistimethate sodium is a prodrug; it is produced by the reaction of colistin with formaldehyde and sodium bisulfite, which leads to the addition of a sulfomethyl group to the primary amines of colistin. Colistimethate sodium is less toxic than colistin when administered parenterally. In aqueous solutions it undergoes hydrolysis to form a complex mixture of partially sulfomethylated derivatives, as well as colistin. Resistance to colistin began to appear as of 2015.

<span class="mw-page-title-main">Ligand (biochemistry)</span> Substance that forms a complex with a biomolecule

In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from Latin ligare, which means 'to bind'. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. The binding typically results in a change of conformational isomerism (conformation) of the target protein. In DNA-ligand binding studies, the ligand can be a small molecule, ion, or protein which binds to the DNA double helix. The relationship between ligand and binding partner is a function of charge, hydrophobicity, and molecular structure.

<span class="mw-page-title-main">CXCR4</span> Protein

C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 is a protein that in humans is encoded by the CXCR4 gene. The protein is a CXC chemokine receptor.

<span class="mw-page-title-main">Metabotropic glutamate receptor</span> Type of glutamate receptor

The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate receptors, mGluRs bind with glutamate, an amino acid that functions as an excitatory neurotransmitter.

<span class="mw-page-title-main">Imipenem</span> Carbapenem antibiotic

Imipenem is a synthetic β-lactam antibiotic belonging to the carbapenems chemical class. developed by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s. Carbapenems are highly resistant to the β-lactamase enzymes produced by many multiple drug-resistant Gram-negative bacteria, thus playing a key role in the treatment of infections not readily treated with other antibiotics. It is usually administered through intravenous injection.

<span class="mw-page-title-main">Sulbactam</span> Chemical compound

Sulbactam is a β-lactamase inhibitor. This drug is given in combination with β-lactam antibiotics to inhibit β-lactamase, an enzyme produced by bacteria that destroys the antibiotics.

<span class="mw-page-title-main">CCL2</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">CCL7</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">CCL11</span> Mammalian protein found in Homo sapiens

C-C motif chemokine 11 also known as eosinophil chemotactic protein and eotaxin-1 is a protein that in humans is encoded by the CCL11 gene. This gene is encoded on three exons and is located on chromosome 17.

<i>Acinetobacter baumannii</i> Species of bacterium

Acinetobacter baumannii is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. It can be an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived (nosocomial) infection. While other species of the genus Acinetobacter are often found in soil samples, it is almost exclusively isolated from hospital environments. Although occasionally it has been found in environmental soil and water samples, its natural habitat is still not known.

CC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane (7-TM) proteins since they span the cell membrane seven times. To date, ten true members of the CC chemokine receptor subfamily have been described. These are named CCR1 to CCR10 according to the IUIS/WHO Subcommittee on Chemokine Nomenclature.

<span class="mw-page-title-main">CCR2</span> Mammalian protein found in Homo sapiens

C-C chemokine receptor type 2 (CCR2 or CD192 is a protein that in humans is encoded by the CCR2 gene. CCR2 is a CC chemokine receptor.

<span class="mw-page-title-main">CCR1</span> Protein in humans

C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.

<span class="mw-page-title-main">Arbekacin</span> Antibiotic

Arbekacin (INN) is a semisynthetic aminoglycoside antibiotic which was derived from kanamycin. It is primarily used for the treatment of infections caused by multi-resistant bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Arbekacin was originally synthesized from dibekacin in 1973 by Hamao Umezawa and collaborators. It has been registered and marketed in Japan since 1990 under the trade name Habekacin. Arbekacin is no longer covered by patent and generic versions of the drug are also available under such trade names as Decontasin and Blubatosine.

<span class="mw-page-title-main">Cenicriviroc</span> Chemical compound

Cenicriviroc is an experimental drug candidate for the treatment of HIV infection and in combination with Tropifexor for non-alcoholic steatohepatitis. It is being developed by Takeda and Tobira Therapeutics.

The Community for Open Antimicrobial Drug Discovery (CO-ADD) is a not-for-profit initiative created in 2015 reaching out to chemists in academia and research organisations who have compounds that were not designed as antibiotics and would not otherwise be screened for antimicrobial activity. These academic compounds are screened against a key panel of drug-resistant bacterial strains -superbugs. Multi-drug resistant microbes are a serious health treat, and exploration of novel chemical diversity is essential to find new antibiotics.

<span class="mw-page-title-main">Halicin</span> Drug and first antibiotic identified by a deep learning algorithm

Halicin (SU-3327) is an experimental drug that acts as an enzyme inhibitor of c-Jun N-terminal kinase (JNK). Originally, it was researched for the treatment of diabetes, but development was discontinued for this application due to poor results in testing. In 2019, this molecule was found by an artificial intelligence (AI) model to show antibiotic properties against a number of bacteria.

The MIT Abdul Latif Jameel Clinic for Machine Learning in Health is a research center at the Massachusetts Institute of Technology (MIT) in the field of artificial intelligence (AI) and health sciences, including disease detection, drug discovery, and the development of medical devices. The MIT Jameel Clinic also supports the commercialization of solutions through grant funding, and has partnered with pharmaceutical companies, like Takeda and Sanofi, and philanthropies, like Community Jameel and Wellcome Trust, to forge collaborations between research and development functions and MIT researchers.

References

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  2. Gallagher J (May 25, 2023). "New superbug-killing antibiotic discovered using AI". BBC News.
  3. Trafton A (25 May 2023). "Using AI, scientists find a drug that could combat drug-resistant infections". MIT News . Retrieved 28 May 2023.
  4. "Scientists use AI to find promising new antibiotic to fight evasive hospital superbug". McMaster University. 25 May 2023.
  5. Clark RD, Caroon JM, Kluge AF, Repke DB, Roszkowski AP, Strosberg AM, et al. (May 1983). "Synthesis and antihypertensive activity of 4'-substituted spiro[4H-3,1-benzoxazine-4,4'-piperidin]-2(1H)-ones". Journal of Medicinal Chemistry. 26 (5): 657–661. doi:10.1021/jm00359a007. PMID   6842505.
  6. Mirzadegan T, Diehl F, Ebi B, Bhakta S, Polsky I, McCarley D, et al. (August 2000). "Identification of the binding site for a novel class of CCR2b chemokine receptor antagonists: binding to a common chemokine receptor motif within the helical bundle". The Journal of Biological Chemistry. 275 (33): 25562–25571. doi: 10.1074/jbc.M000692200 . PMID   10770925.
  7. Rehni AK, Singh N (March 2012). "Ammonium pyrrolidine dithiocarbamate and RS 102895 attenuate opioid withdrawal in vivo and in vitro". Psychopharmacology. 220 (2): 427–438. doi:10.1007/s00213-011-2489-8. PMID   21931991. S2CID   253752924.
  8. Yuan F, Yosef N, Lakshmana Reddy C, Huang A, Chiang SC, Tithi HR, Ubogu EE (2014). "CCR2 gene deletion and pharmacologic blockade ameliorate a severe murine experimental autoimmune neuritis model of Guillain-Barré syndrome". PLOS ONE. 9 (3): e90463. Bibcode:2014PLoSO...990463Y. doi: 10.1371/journal.pone.0090463 . PMC   3954548 . PMID   24632828.
  9. Alsheikh AJ, Dasinger JH, Abais-Battad JM, Fehrenbach DJ, Yang C, Cowley AW, Mattson DL (April 2020). "CCL2 mediates early renal leukocyte infiltration during salt-sensitive hypertension". American Journal of Physiology. Renal Physiology. 318 (4): F982–F993. doi:10.1152/ajprenal.00521.2019. PMC   7191447 . PMID   32150444.
  10. Coy P (2023-11-24). "Opinion | What Am I Thankful for This Year? Amazing Scientific Discoveries". The New York Times. ISSN   0362-4331 . Retrieved 2023-11-26.