Inhibition of horseradish peroxidase catalytic activity by new 3-phenylcoumarin derivatives: synthesis and structure-activity relationships.
Twenty hydroxylated and acetoxylated 3-phenylcoumarins were synthesized, and the structure-activity relationships were investigated by evaluating the ability of these compounds to modulate horseradish peroxidase (HRP) catalytic activity and comparing the results to four flavonoids (quercetin, myricetin, kaempferol and galangin), previously reported as HRP inhibitors. It was observed that 3-phenylcoumarins bearing a catechol group were as active as quercetin and myricetin, which also show this substituent in the B-ring. The presence of 6,2'-dihydroxy group or 6,7,3',4'-tetraacetoxy group in the 3-phenylcoumarin structure also contributed to a significant inhibitory effect on the HRP activity. The catechol-containing 3-phenylcoumarin derivatives also showed free radical scavenger activity. Molecular modeling studies by docking suggested that interactions between the heme group in the HRP active site and the catechol group linked to the flavonoid B-ring or to the 3-phenyl coumarin ring are important to inhibit enzyme catalytic activity.
Kabeya
Luciana M
LM
Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto da Universidade de São Paulo, Av. Café s/n(o), Ribeirão Preto-SP, CEP 14040-903, Brazil.
de Marchi
Anderson A
AA
Kanashiro
Alexandre
A
Lopes
Norberto P
NP
da Silva
Carlos H T P
CH
Pupo
Mônica T
MT
Lucisano-Valim
Yara M
YM
D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006735:Horseradish Peroxidase / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D003374:Coumarins; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D006735:Horseradish Peroxidase