Fabimycin

Last updated
Fabimycin
Fabimycin.svg
Names
IUPAC name
(E)-3-(7-amino-8-oxo-5,6,7,9-tetrahydropyrido[2,3-b]azepin-3-yl)-N-methyl-N-[(3-methyl-1-benzofuran-2-yl)methyl]prop-2-enamide
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
  • InChI=1S/C23H24N4O3/c1-14-17-5-3-4-6-19(17)30-20(14)13-27(2)21(28)10-7-15-11-16-8-9-18(24)23(29)26-22(16)25-12-15/h3-7,10-12,18H,8-9,13,24H2,1-2H3,(H,25,26,29)/b10-7+
    Key: ZWQNEFFHBSGFHV-JXMROGBWSA-N
  • CN(CC1=C(C)C2=CC=CC=C2O1)C(=O)\C=C\C1=CC2=C(NC(=O)C(N)CC2)N=C1
Properties
C23H24N4O3
Molar mass 404.470 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Fabimycin is an newly developed antibiotic candidate which is effective against gram-negative bacterias, an unusually problematic class of bacteria that uses thicker cell walls and molecular efflux pumps to protect themselves by preventing the antibiotics reaching inside the cells. [1] [2]

Contents

Antibiotic resistance

Global deaths attributable to antimicrobial resistance (AMR) numbered 1.27 million in 2019. That year, AMR may have contributed to 5 million deaths and one in five people who died due to AMR were children under five years old. [3] The European Centre for Disease Prevention and Control calculated that in 2015 there were 671,689 infections in the EU and European Economic Area caused by antibiotic-resistant bacteria, resulting in 33,110 deaths. Most were acquired in healthcare settings. [4]

History

Researchers modified the structure of Debio-1452, [5] an under-development antibiotic that is active against gram positive bacteria, and its derivative, which is moderately effective against non-resistant gram-negative bacteria. [1] [6] The drug inhibits the bacterial enzyme enoyl-acyl carrier protein reductase (FabI), which is an important enzyme in bacterial fatty acid biosynthesis. Clinical trials targeting the enzyme for use in S. aureus (Gram +ve) infections have reached Phase 2 inhibitors. [2]

Fabimycin was tested in mice against more than 200 colonies of resistant bacteria, across 54 strains of E. coli, Klebsiella pneumoniae and Acinetobacter baumannii . It cleared up pneumonia and urinary tract infections, pushing bacteria levels lower than before infection in mouse models. [1]

Further, it did not affect some types of commensal bacteria present in the gut microbiome. [1]

See also

References

  1. 1 2 3 4 Irving, Michael (2022-08-11). "New antibiotic molecule kills dozens of the toughest types of superbugs". New Atlas. Retrieved 2022-08-11.
  2. 1 2 Parker, Erica N.; Cain, Brett N.; Hajian, Behnoush; Ulrich, Rebecca J.; Geddes, Emily J.; Barkho, Sulyman; Lee, Hyang Yeon; Williams, John D.; Raynor, Malik; Caridha, Diana; Zaino, Angela; Shekhar, Mrinal; Muñoz, Kristen A.; Rzasa, Kara M.; Temple, Emily R. (2022-08-10). "An Iterative Approach Guides Discovery of the FabI Inhibitor Fabimycin, a Late-Stage Antibiotic Candidate with In Vivo Efficacy against Drug-Resistant Gram-Negative Infections". ACS Central Science. 8 (8): 1145–1158. doi:10.1021/acscentsci.2c00598. ISSN   2374-7943. PMC   9413440 . PMID   36032774.
  3. ↑ Murray, Christopher JL; Ikuta, Kevin Shunji; Sharara, Fablina; Swetschinski, Lucien; Aguilar, Gisela Robles; Gray, Authia; Han, Chieh; Bisignano, Catherine; Rao, Puja; Wool, Eve; Johnson, Sarah C. (2022-01-19). "Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis". The Lancet. 399 (10325): 629–655. doi:10.1016/S0140-6736(21)02724-0. ISSN   0140-6736. PMC   8841637 . PMID   35065702. S2CID   246077406.
  4. ↑ "Antibiotic-resistant bacteria responsible for over 33,000 deaths in Europe in 2015, study finds". Pharmaceutical Journal. 7 November 2018. Archived from the original on 7 October 2019. Retrieved 16 December 2018.
  5. ↑ Flamm, Robert K.; Rhomberg, Paul R.; Kaplan, Nachum; Jones, Ronald N.; Farrell, David J. (May 2015). "Activity of Debio1452, a FabI inhibitor with potent activity against Staphylococcus aureus and coagulase-negative Staphylococcus spp., including multidrug-resistant strains". Antimicrobial Agents and Chemotherapy. 59 (5): 2583–2587. doi:10.1128/AAC.05119-14. ISSN   1098-6596. PMC   4394798 . PMID   25691627.
  6. ↑ Davis, Joe (2022-08-11). "Antibiotic-resistant bacteria: New drug can fight off 300 different types of superbugs". timetotimes.com. Retrieved 2022-08-11.

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