Synthesis and biological evaluation of tetrahydroisoquinoline-derived antibacterial compounds.

Payne, M; Bottomley, AL; Och, A; Hiscocks, HG; Asmara, AP; Harry, EJ; Ung, AT

Synthesis and biological evaluation of tetrahydroisoquinoline-derived antibacterial compounds.

Payne, M Bottomley, AL Och, A Hiscocks, HG Asmara, AP Harry, EJ Ung, AT

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Publisher:: PERGAMON-ELSEVIER SCIENCE LTD
Publication Type:: Journal Article
Citation:: Bioorg Med Chem, 2022, 57, pp. 116648
Issue Date:: 2022-03-01

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Field	Value	Language
dc.contributor.author	Payne, M
dc.contributor.author	Bottomley, AL
dc.contributor.author	Och, A
dc.contributor.author	Hiscocks, HG
dc.contributor.author	Asmara, AP
dc.contributor.author	Harry, EJ
dc.contributor.author	Ung, AT
dc.date.accessioned	2022-03-31T23:30:51Z
dc.date.available	2022-01-26
dc.date.available	2022-03-31T23:30:51Z
dc.date.issued	2022-03-01
dc.identifier.citation	Bioorg Med Chem, 2022, 57, pp. 116648
dc.identifier.issn	0968-0896
dc.identifier.issn	1464-3391
dc.identifier.uri	http://hdl.handle.net/10453/155821
dc.description.abstract	Antibiotic resistance is one of the greatest threats to modern medicine. Drugs that were once routinely used to treat infections are being rendered ineffective, increasing the demand for novel antibiotics with low potential for resistance. Here we report the synthesis of 18 novel cationic tetrahydroisoquinoline-triazole compounds. Five of the developed molecules were active against S. aureus at a low MIC of 2-4 μg/mL. Hit compound 4b was also found to eliminate M. tuberculosis H37Rv at MIC of 6 μg/mL. This potent molecule was found to eliminate S. aureus effectively, with no resistance observed after thirty days of sequential passaging. These results identified compound 4b and its analogues as potential candidates for further drug development that could help tackle the threat of antibiotic resistance.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	PERGAMON-ELSEVIER SCIENCE LTD
dc.relation.ispartof	Bioorg Med Chem
dc.relation.isbasedon	10.1016/j.bmc.2022.116648
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	Medicinal & Biomolecular Chemistry
dc.subject.mesh	Anti-Bacterial Agents
dc.subject.mesh	Dose-Response Relationship, Drug
dc.subject.mesh	Microbial Sensitivity Tests
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Mycobacterium tuberculosis
dc.subject.mesh	Staphylococcus aureus
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Tetrahydroisoquinolines
dc.subject.mesh	Mycobacterium tuberculosis
dc.subject.mesh	Staphylococcus aureus
dc.subject.mesh	Tetrahydroisoquinolines
dc.subject.mesh	Anti-Bacterial Agents
dc.subject.mesh	Microbial Sensitivity Tests
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Dose-Response Relationship, Drug
dc.title	Synthesis and biological evaluation of tetrahydroisoquinoline-derived antibacterial compounds.
dc.type	Journal Article
utslib.citation.volume	57
utslib.location.activity	England
utslib.for	0304 Medicinal and Biomolecular Chemistry
utslib.for	0305 Organic Chemistry
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CCET - Centre for Clean Energy Technology
utslib.copyright.status	closed_access	*
dc.date.updated	2022-03-31T23:30:49Z
pubs.publication-status	Published
pubs.volume	57

Abstract:

Antibiotic resistance is one of the greatest threats to modern medicine. Drugs that were once routinely used to treat infections are being rendered ineffective, increasing the demand for novel antibiotics with low potential for resistance. Here we report the synthesis of 18 novel cationic tetrahydroisoquinoline-triazole compounds. Five of the developed molecules were active against S. aureus at a low MIC of 2-4 μg/mL. Hit compound 4b was also found to eliminate M. tuberculosis H37Rv at MIC of 6 μg/mL. This potent molecule was found to eliminate S. aureus effectively, with no resistance observed after thirty days of sequential passaging. These results identified compound 4b and its analogues as potential candidates for further drug development that could help tackle the threat of antibiotic resistance.

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http://hdl.handle.net/10453/155821