Synthesis and biological evaluation of pyrrole-based chalcones as CYP1 enzyme inhibitors, for possible prevention of cancer and overcoming cisplatin resistance

Simple item page
dc.cclicenceCC-BY-NCen
dc.contributor.authorWilliams, Ibidapo Stevenen
dc.contributor.authorJoshi, Prashanten
dc.contributor.authorGatchie, Lindaen
dc.contributor.authorSharma, M.en
dc.contributor.authorSatti, N. K.en
dc.contributor.authorVishwakarma, R. A.en
dc.contributor.authorChaudhuri, Bhabatoshen
dc.contributor.authorBharate, Sandip B.en
dc.date.acceptance2017-07-23en
dc.date.accessioned2018-02-13T12:26:46Z
dc.date.available2018-02-13T12:26:46Z
dc.date.issued2017-07-04
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.abstractInhibitors of CYP1 enzymes may play vital roles in the prevention of cancer and overcoming chemo-resistance to anticancer drugs. In this letter, we report synthesis of twenty-three pyrrole based heterocyclic chalcones which were screened for inhibition of CYP1 isoforms. Compound 3n potently inhibited CYP1B1 with an IC50 of 0.2 lM in SacchrosomesTM and CYP1B1-expressing live human cells. However, compound 3j which inhibited both CYP1A1 and CYP1B1 with an IC50 of 0.9 mM, using the same systems, also potently antagonized B[a]P-mediated induction of AhR signaling in yeast (IC50, 1.5 mM), fully protected human cells from B[a]P toxicity and completely reversed cisplatin resistance in human cells that overexpress CYP1B1 by restoring cisplatin’s cytotoxicity. Molecular modeling studies were performed to rationalize the observed potency and selectivity of enzyme inhibition by compounds 3j and 3n.en
dc.funderCYP Design Limited, Innovation Centre, 49 Oxford Street, Leicester LE1 5XY, UKen
dc.identifier.citationWilliams, I.S. et al. (2017) Synthesis and biological evaluation of pyrrole-based chalcones as CYP1 enzyme inhibitors, for possible prevention of cancer and overcoming cisplatin resistance. Bioorganic & Medicinal Chemistry Letters, 27(16), pp.3683-3687.en
dc.identifier.doihttps://doi.org/10.1016/j.bmcl.2017.07.010
dc.identifier.issn0960-894X
dc.identifier.issn1464-3405
dc.identifier.urihttp://hdl.handle.net/2086/15198
dc.language.isoenen
dc.peerreviewedYesen
dc.projectidN/Aen
dc.publisherElsevieren
dc.subjectHeterocyclic chalconesen
dc.subjectAhR antagonismen
dc.subjectCYP1A1en
dc.subjectChemopreventionen
dc.subjectCYP1B1en
dc.subjectCisplatin chemo-resistanceen
dc.titleSynthesis and biological evaluation of pyrrole-based chalcones as CYP1 enzyme inhibitors, for possible prevention of cancer and overcoming cisplatin resistanceen
dc.typeArticleen

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
BMCL (Pyrrole-based chalcones).pdf
Size:
708.91 KB
Format:
Adobe Portable Document Format
Description:
Main article
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
4.2 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

School of Allied Health Sciences