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dc.contributor.authorHouston, Sevan D
dc.contributor.authorFahrenhorst-Jones, Tyler
dc.contributor.authorXing, Hui
dc.contributor.authorChalmers, Benjamin A
dc.contributor.authorSykes, Melissa L
dc.contributor.authorStok, Jeanette E
dc.contributor.authorSoto, Clementina Farfan
dc.contributor.authorBurns, Jed M
dc.contributor.authorBernhardt, Paul
dc.contributor.authorDe Voss, James J
dc.contributor.authorBoyle, Glen M
dc.contributor.authorSmith, Maree T
dc.contributor.authorTsanaktsidis, John
dc.contributor.authorSavage, G Paul
dc.contributor.authorAvery, Vicky M
dc.contributor.authorWilliams, Craig M
dc.date.accessioned2019-10-14T04:46:20Z
dc.date.available2019-10-14T04:46:20Z
dc.date.issued2019
dc.identifier.issn1477-0520
dc.identifier.doi10.1039/c9ob01238a
dc.identifier.urihttp://hdl.handle.net/10072/388386
dc.description.abstractThe cubane phenyl ring bioisostere paradigm was further explored in an extensive study covering a wide range of pharmaceutical and agrochemical templates, which included antibiotics (cefaclor, penicillin G) and antihistamine (diphenhydramine), a smooth muscle relaxant (alverine), an anaesthetic (ketamine), an agrochemical instecticide (triflumuron), an antiparasitic (benznidazole) and an anticancer agent (tamibarotene). This investigation highlights the scope and limitations of incorporating cubane into bioactive molecule discovery, both in terms of synthetic compatibility and physical property matching. Cubane maintained bioisosterism in the case of the Chagas disease antiparasitic benznidazole, although it was less active in the case of the anticancer agent (tamibarotenne). Application of the cyclooctatetraene (COT) (bio)motif complement was found to optimize benznidazole relative to the benzene parent, and augmented anticancer activity relative to the cubane analogue in the case of tamibarotene. Like all bioisosteres, scaffolds and biomotifs, however, there are limitations (e.g. synthetic implementation), and these have been specifically highlighted herein using failed examples. A summary of all templates prepared to date by our group that were biologically evaluated strongly supports the concept that cubane is a valuable tool in bioactive molecule discovery and COT is a viable complement.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherRoyal Society of Chemistry
dc.relation.ispartofpagefrom6790
dc.relation.ispartofpageto6798
dc.relation.ispartofissue28
dc.relation.ispartofjournalOrganic & Biomolecular Chemistry
dc.relation.ispartofvolume17
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry
dc.subject.fieldofresearchOrganic Chemistry
dc.subject.fieldofresearchcode0304
dc.subject.fieldofresearchcode0305
dc.subject.keywordsScience & Technology
dc.subject.keywordsPhysical Sciences
dc.subject.keywordsChemistry
dc.subject.keywordsSYSTEMATIC SUBSTITUTION
dc.titleThe cubane paradigm in bioactive molecule discovery: further scope, limitations and the cyclooctatetraene complement
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationHouston, SD; Fahrenhorst-Jones, T; Xing, H; Chalmers, BA; Sykes, ML; Stok, JE; Soto, CF; Burns, JM; Bernhardt, P; De Voss, JJ; Boyle, GM; Smith, MT; Tsanaktsidis, J; Savage, GP; Avery, VM; Williams, CM, The cubane paradigm in bioactive molecule discovery: further scope, limitations and the cyclooctatetraene complement, Organic & Biomolecular Chemistry, 2019, 17 (28), pp. 6790-6798
dc.date.updated2019-10-14T04:43:35Z
gro.hasfulltextNo Full Text
gro.griffith.authorAvery, Vicky M.
gro.griffith.authorSykes, Melissa L.


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