Cytochrome P450 1 enzyme inhibition and anticancer potential of chromene amides from Amyris plumieri.
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.
Badal
S
S
Natural Products Institute, Faculty of Pure and Applied Sciences, University of the West Indies, Mona, Jamaica.
Williams
S A
SA
Huang
G
G
Francis
S
S
Vedantam
P
P
Vendantam
P
P
Dunbar
O
O
Jacobs
H
H
Tzeng
T J
TJ
Gangemi
J
J
Delgoda
R
R
D000081:Acetamides / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D000577:Amides / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D001578:Benzopyrans / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D027821:Rutaceae / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000081:Acetamides; D000577:Amides; D000972:Antineoplastic Agents, Phytogenic; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D019363:Cytochrome P-450 CYP1A1