Abaucin

Abaucin
Identifiers
	IUPAC name 1'-[2-[4-(trifluoromethyl)phenyl]ethyl]spiro[1H-3,1-benzoxazine-4,4'-piperidine]-2-one;
CAS Number	300815-41-2 ; 1173022-16-6 (hydrochloride);
PubChem CID	10000456;
IUPHAR/BPS	779;
ChemSpider	8176037;
ChEBI	CHEBI:93458;
ChEMBL	ChEMBL1593104;
Chemical and physical data
Formula	C21H21F3N2O2
Molar mass	390.406 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1CN(CCC12C3=CC=CC=C3NC(=O)O2)CCC4=CC=C(C=C4)C(F)(F)F;
	InChI 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 3 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]

References[edit]

^ Liu G, Catacutan DB, Rathod K, Swanson K, Jin W, Mohammed JC, et al. (May 2023). "Deep learning-guided discovery of an antibiotic targeting Acinetobacter baumannii". Nature Chemical Biology. doi:10.1038/s41589-023-01349-8. PMID 37231267. S2CID 258909341.
^ Gallagher J (May 25, 2023). "New superbug-killing antibiotic discovered using AI". BBC News.
^ Trafton A (25 May 2023). "Using AI, scientists find a drug that could combat drug-resistant infections". MIT News. Retrieved 28 May 2023.
^ "Scientists use AI to find promising new antibiotic to fight evasive hospital superbug". McMaster University. 25 May 2023.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

[pmid37231267-1] Liu G, Catacutan DB, Rathod K, Swanson K, Jin W, Mohammed JC, et al. (May 2023). "Deep learning-guided discovery of an antibiotic targeting Acinetobacter baumannii". Nature Chemical Biology. doi:10.1038/s41589-023-01349-8. PMID 37231267. S2CID 258909341.

[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.

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