Cytochrome P450 1 enzyme inhibition and anticancer potential of chromene amides from Amyris plumieri

S Badal; S A Williams; G Huang; S Francis; P Vedantam; O Dunbar; H Jacobs; T J Tzeng; J Gangemi; R Delgoda

doi:10.1016/j.fitote.2010.10.003

Cytochrome P450 1 enzyme inhibition and anticancer potential of chromene amides from Amyris plumieri

Fitoterapia. 2011 Mar;82(2):230-6. doi: 10.1016/j.fitote.2010.10.003. Epub 2010 Oct 13.

Authors

S Badal¹, S A Williams, G Huang, S Francis, P Vedantam, O Dunbar, H Jacobs, T J Tzeng, J Gangemi, R Delgoda

Affiliation

¹ Natural Products Institute, Faculty of Pure and Applied Sciences, University of the West Indies, Mona, Jamaica.

PMID: 20951188
DOI: 10.1016/j.fitote.2010.10.003

Abstract

Cytochrome P450 (CYP) enzyme inhibitory properties of six chromenylated amide compounds (CAs) from Amyris plumieri are described. Inhibition of CYP microsomes (CYP1A1, CYP1A2, CYP1B1, CYP2D6, CYP3A4 and CYP2C19) was monitored using a fluorescent assay. Potent inhibition was found against CYP1A1 with IC(50) and K(i) for CA1 (acetamide), being the lowest at 1.547 ± 1.0 μM and 0.37 μM respectively, displaying non-competitive kinetics. The selectivity for CYP1A1 was increased in CA3 (butanamide), which also exhibited cytotoxicity against breast cancer cells, MCF7 with an IC(50) of 47.46 ± 1.62 μM. Structure-activity relationship studies provide insight at a molecular level for CAs with implications in chemoprevention and chemotherapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetamides / isolation & purification
Acetamides / pharmacology
Acetamides / therapeutic use
Amides / isolation & purification
Amides / pharmacology
Amides / therapeutic use*
Antineoplastic Agents, Phytogenic / isolation & purification
Antineoplastic Agents, Phytogenic / pharmacology
Antineoplastic Agents, Phytogenic / therapeutic use*
Benzopyrans / isolation & purification
Benzopyrans / pharmacology
Benzopyrans / therapeutic use
Breast Neoplasms / drug therapy*
Cytochrome P-450 CYP1A1 / antagonists & inhibitors*
Enzyme Inhibitors / isolation & purification
Enzyme Inhibitors / pharmacology
Enzyme Inhibitors / therapeutic use
Female
Humans
Phytotherapy*
Plant Extracts / isolation & purification
Plant Extracts / pharmacology
Plant Extracts / therapeutic use*
Rutaceae / chemistry*
Structure-Activity Relationship

Substances

Acetamides
Amides
Antineoplastic Agents, Phytogenic
Benzopyrans
Enzyme Inhibitors
Plant Extracts
Cytochrome P-450 CYP1A1