anti-Tuberculosis natural products: synthesis and biological evaluation of pyridoacridine alkaloids related to ascididemin

Appleton, DR; Pearce, Allison; Copp, Brent

dc.contributor.author	Appleton, DR	en
dc.contributor.author	Pearce, Allison	en
dc.contributor.author	Copp, Brent	en
dc.date.accessioned	2017-10-23T23:44:58Z	en
dc.date.available	2010-05-10	en
dc.date.issued	2010-07-03	en
dc.identifier.citation	Tetrahedron, 66(27-28):4977-4986, 03 Jul 2010	en
dc.identifier.issn	0040-4020	en
dc.identifier.uri	http://hdl.handle.net/2292/36198	en
dc.description.abstract	There is an urgent need for novel therapeutics possessing new modes of action to treat tuberculosis (TB) infections. In this study we report on the synthesis and biological evaluation of a series of pyrido[2,3,4-kl]acridin-6-one alkaloids related to the anti-TB (MIC 0.35 μM) but cytotoxic (IC50 <0.14 μM) marine natural product ascididemin (1). The most interesting compounds identified were 21 and 24, which were found to inhibit the growth of Mycobacterium tuberculosis (Mtb) H37Rv with MIC 2.0 μM, but with negligible cytotoxicity towards Vero and P388 cells (IC50>25 μM). Another analogue (10) was evaluated against a range of singly-drug-resistant strains of Mtb and was found to exhibit no cross-resistance. These results suggest that the pyrido[2,3,4-kl]acridin-6-one skeleton may provide a useful scaffold for future studies directed towards possible anti-TB drugs.	en
dc.description.uri	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000279126700009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=6e41486220adb198d0efde5a3b153e7d	en
dc.language	English	en
dc.publisher	Elsevier	en
dc.relation.ispartofseries	Tetrahedron	en
dc.rights	Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://sherpa.ac.uk/romeo/issn/0040-4020/ https://www.elsevier.com/about/our-business/policies/sharing	en
dc.rights.uri	https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm	en
dc.subject	Science & Technology	en
dc.subject	Physical Sciences	en
dc.subject	Chemistry, Organic	en
dc.subject	Chemistry	en
dc.subject	CHEMISTRY, ORGANIC	en
dc.subject	Tuberculosis	en
dc.subject	Natural Products	en
dc.subject	Ascididemin	en
dc.subject	pyridoacridine	en
dc.subject	MYCOBACTERIUM-TUBERCULOSIS	en
dc.subject	TUNICATE	en
dc.subject	CONVENIENT	en
dc.subject	INHIBITORS	en
dc.subject	QUINONES	en
dc.subject	ANALOGS	en
dc.subject	DNA	en
dc.title	anti-Tuberculosis natural products: synthesis and biological evaluation of pyridoacridine alkaloids related to ascididemin	en
dc.type	Journal Article	en
dc.identifier.doi	10.1016/j.tet.2010.05.033	en
pubs.issue	27-28	en
pubs.begin-page	4977	en
pubs.volume	66	en
dc.rights.holder	Copyright: Elsevier	en
pubs.author-url	http://www.sciencedirect.com/science/article/pii/S0040402010007702	en
pubs.end-page	4986	en
pubs.publication-status	Published	en
dc.rights.accessrights	http://purl.org/eprint/accessRights/RestrictedAccess	en
pubs.subtype	Article	en
pubs.elements-id	119725	en
pubs.org-id	Science	en
pubs.org-id	Chemistry	en
pubs.org-id	Science Research	en
pubs.org-id	Maurice Wilkins Centre (2010-2014)	en
dc.identifier.eissn	1464-5416	en
pubs.record-created-at-source-date	2017-10-24	en
pubs.online-publication-date	2010-06-01	en