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(E)-3-(3,4,5-Trimethoxyphenyl)-1-(pyridin-4-yl)prop-2-en-1-one, a heterocyclic chalcone is a potent and selective CYP1A1 inhibitor and cancer chemopreventive agent

Horley, Neill J.; Beresford, Kenneth J.M.; Kaduskar, Supriya; Joshi, Prashant; McCann, Glen J.P.; Ruparelia, Ketan C.; Williams, Ibidapo S.; Gatchie, Linda; Sonawane, Vinay R.; Bharate, Sandip B.; Chaudhuri, Bhabatosh


Neill J. Horley

Kenneth J.M. Beresford

Supriya Kaduskar

Prashant Joshi

Glen J.P. McCann

Ketan C. Ruparelia

Ibidapo Williams
Research Fellow- Cell Cultural Monitoring Technology

Linda Gatchie

Vinay R. Sonawane

Sandip B. Bharate

Bhabatosh Chaudhuri


The 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 Sacchrosomes™ and live human HEK293 cells. The structure-activity relationship analysis indicated that chalcones bearing tri-alkoxy groups (8a and 8k) on non-heterocyclic 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 sub-family 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.


Horley, N. J., Beresford, K. J., Kaduskar, S., Joshi, P., McCann, G. J., Ruparelia, K. C., …Chaudhuri, B. (2017). (E)-3-(3,4,5-Trimethoxyphenyl)-1-(pyridin-4-yl)prop-2-en-1-one, a heterocyclic chalcone is a potent and selective CYP1A1 inhibitor and cancer chemopreventive agent. Bioorganic and Medicinal Chemistry Letters, 27(24), 5409-5414.

Journal Article Type Article
Acceptance Date Nov 5, 2017
Online Publication Date Nov 6, 2017
Publication Date Dec 15, 2017
Deposit Date May 9, 2018
Journal Bioorganic and Medicinal Chemistry Letters
Print ISSN 0960-894X
Electronic ISSN 1464-3405
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 27
Issue 24
Pages 5409-5414
Keywords Chalcones, CYP1A1, Cancer chemoprevention, B[a]P, AhR antagonism
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