Antitubercular Bis-Substituted Cyclam Derivatives: Structure-Activity Relationships and in Vivo Studies.

Spain, M; Wong, JK-H; Nagalingam, G; Batten, JM; Hortle, E; Oehlers, SH; Jiang, XF; Murage, HE; Orford, JT; Crisologo, P; Triccas, JA; Rutledge, PJ; Todd, MH

Antitubercular Bis-Substituted Cyclam Derivatives: Structure-Activity Relationships and in Vivo Studies.

Spain, M Wong, JK-H Nagalingam, G Batten, JM Hortle, E

Oehlers, SH Jiang, XF Murage, HE Orford, JT Crisologo, P Triccas, JA Rutledge, PJ Todd, MH

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Publisher:: American Chemical Society
Publication Type:: Journal Article
Citation:: Journal of Medicinal Chemistry, 2018, 61, (8), pp. 3595-3608
Issue Date:: 2018-04-26

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Field	Value	Language
dc.contributor.author	Spain, M
dc.contributor.author	Wong, JK-H
dc.contributor.author	Nagalingam, G
dc.contributor.author	Batten, JM
dc.contributor.author	Hortle, E https://orcid.org/0000-0001-9633-5638
dc.contributor.author	Oehlers, SH
dc.contributor.author	Jiang, XF
dc.contributor.author	Murage, HE
dc.contributor.author	Orford, JT
dc.contributor.author	Crisologo, P
dc.contributor.author	Triccas, JA
dc.contributor.author	Rutledge, PJ
dc.contributor.author	Todd, MH
dc.date.accessioned	2022-08-23T02:33:57Z
dc.date.available	2022-08-23T02:33:57Z
dc.date.issued	2018-04-26
dc.identifier.citation	Journal of Medicinal Chemistry, 2018, 61, (8), pp. 3595-3608
dc.identifier.issn	0022-2623
dc.identifier.issn	1520-4804
dc.identifier.uri	http://hdl.handle.net/10453/160720
dc.description.abstract	We recently reported the discovery of nontoxic cyclam-derived compounds that are active against drug-resistant Mycobacterium tuberculosis. In this paper we report exploration of the structure-activity relationship for this class of compounds, identifying several simpler compounds with comparable activity. The most promising compound identified, possessing significantly improved water solubility, displayed high levels of bacterial clearance in an in vivo zebrafish embryo model, suggesting this compound series has promise for in vivo treatment of tuberculosis.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	American Chemical Society
dc.relation	http://purl.org/au-research/grants/nhmrc/1043225
dc.relation.ispartof	Journal of Medicinal Chemistry
dc.relation.isbasedon	10.1021/acs.jmedchem.7b01569
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	Animals
dc.subject.mesh	Antitubercular Agents
dc.subject.mesh	Aza Compounds
dc.subject.mesh	Bacterial Load
dc.subject.mesh	Coordination Complexes
dc.subject.mesh	Drug Resistance, Bacterial
dc.subject.mesh	Heterocyclic Compounds, 1-Ring
dc.subject.mesh	Macrocyclic Compounds
dc.subject.mesh	Metals, Heavy
dc.subject.mesh	Microbial Sensitivity Tests
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Mycobacterium marinum
dc.subject.mesh	Solubility
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Tuberculosis
dc.subject.mesh	Zebrafish
dc.subject.mesh	Animals
dc.subject.mesh	Antitubercular Agents
dc.subject.mesh	Aza Compounds
dc.subject.mesh	Bacterial Load
dc.subject.mesh	Coordination Complexes
dc.subject.mesh	Drug Resistance, Bacterial
dc.subject.mesh	Heterocyclic Compounds, 1-Ring
dc.subject.mesh	Macrocyclic Compounds
dc.subject.mesh	Metals, Heavy
dc.subject.mesh	Microbial Sensitivity Tests
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Mycobacterium marinum
dc.subject.mesh	Solubility
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Tuberculosis
dc.subject.mesh	Zebrafish
dc.subject.mesh	Animals
dc.subject.mesh	Zebrafish
dc.subject.mesh	Mycobacterium marinum
dc.subject.mesh	Tuberculosis
dc.subject.mesh	Metals, Heavy
dc.subject.mesh	Aza Compounds
dc.subject.mesh	Heterocyclic Compounds, 1-Ring
dc.subject.mesh	Macrocyclic Compounds
dc.subject.mesh	Antitubercular Agents
dc.subject.mesh	Microbial Sensitivity Tests
dc.subject.mesh	Drug Resistance, Bacterial
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Solubility
dc.subject.mesh	Coordination Complexes
dc.subject.mesh	Bacterial Load
dc.title	Antitubercular Bis-Substituted Cyclam Derivatives: Structure-Activity Relationships and in Vivo Studies.
dc.type	Journal Article
utslib.citation.volume	61
utslib.location.activity	United States
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/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2022-08-23T02:33:56Z
pubs.issue	8
pubs.publication-status	Published
pubs.volume	61
utslib.citation.issue	8

Abstract:

We recently reported the discovery of nontoxic cyclam-derived compounds that are active against drug-resistant Mycobacterium tuberculosis. In this paper we report exploration of the structure-activity relationship for this class of compounds, identifying several simpler compounds with comparable activity. The most promising compound identified, possessing significantly improved water solubility, displayed high levels of bacterial clearance in an in vivo zebrafish embryo model, suggesting this compound series has promise for in vivo treatment of tuberculosis.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/160720