Show simple item record

dc.contributor.authorHorley, Neillen
dc.contributor.authorBeresford, Kenneth J. M.en
dc.contributor.authorKaduskar, S.en
dc.contributor.authorJoshi, Prashanten
dc.contributor.authorMcCann, Glen J. P.en
dc.contributor.authorRuparelia, K. C.en
dc.contributor.authorWilliams, Ibidapo Stevenen
dc.contributor.authorGatchie, Lindaen
dc.contributor.authorSonawane, Vinayen
dc.contributor.authorBharate, Sandip B.en
dc.contributor.authorChaudhuri, Bhabatoshen
dc.date.accessioned2018-02-13T08:55:30Z
dc.date.available2018-02-13T08:55:30Z
dc.date.issued2017-11-06
dc.identifier.citationHorley, N. et al. (2017) (E)-3-(3,4,5-Trimethoxyphenyl)-1-(pyridin-4-yl)prop-2-en-1-one, a heterocyclic chalconeis a potent and selective CYP1A1 inhibitor and cancer chemopreventative agent. Bioorganic and Medicinal Chemistry Letters, 27(24), pp.5409-5414.en
dc.identifier.urihttp://hdl.handle.net/2086/15192
dc.descriptionThe file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI linken
dc.description.abstractThe overexpression of CYP1 family of enzymes is reported to be associated with development of human carcinomas. It has been well reported that CYP1A1 specific inhibitors prevents carcinogenesis. Herein, thirteen pyridine-4-yl series of chalcones were synthesized and screened for inhibition of CYP1 isoforms 1A1, 1B1 and 1A2 in SacchrosomesTM and live human HEK293 cells. The structure-activity relationship analysis indicated that chalcones bearing tri-alkoxy groups (8a and 8k) on nonheterocyclic ring displayed selective inhibition of CYP1A1 enzyme, with IC50 values of 58 and 65 nM, respectively. The 3,4,5-trimethoxy substituted derivative 8a have shown >10 fold selectivity towards CYP1A1 with respect to other enzymes of the CYP1 subfamily and >100-fold selectivity with respect to CYP2 and CYP3 family of enzymes. The potent and selective CYP1A1 inhibitor 8a displayed antagonism of B[a]P mediated activation of aromatic hydrocarbon receptor (AhR) in yeast cells, and also protected human cells from CYP1A1-mediated B[a]P toxicity in human cells. This potent and selective inhibitor of CYP1A1 enzyme have a potential for development as cancer chemopreventive agent.en
dc.language.isoenen
dc.publisherElsevieren
dc.subjectChalconesen
dc.subjectcancer chemopreventionen
dc.subjectB[a}Pen
dc.subjectAhR antagonismen
dc.title(E)-3-(3,4,5-Trimethoxyphenyl)-1-(pyridin-4-yl)prop-2-en-1-one, a heterocyclic chalconeis a potent and selectiveCYP1A1 inhibitor and cancerchemopreventative agenten
dc.typeArticleen
dc.identifier.doihttps://doi.org/10.1016/j.bmcl.2017.11.009
dc.peerreviewedYesen
dc.funderUK Higher Education Innovation Funden
dc.projectidN/Aen
dc.cclicenceCC-BY-NCen
dc.date.acceptance2017-11-05en
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en
dc.exception.ref2021codes254ben


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record