Synthesis and structure-activity relationship study of deoxybenzoins on relaxing effects of porcine coronary artery.
Deoxybenzoins are potent antioxidants and tyrosinase inhibitors with potential to be developed as food preservatives and cosmetic ingredients. To explore the potential in cardiovascular protection, 25 polyphenolic deoxybenzoins were synthesized and evaluated for inhibitory effects on KCl-induced porcine coronary arterial contraction. The results revealed deoxybenzoins are significant inhibitors of KCl-induced arterial contraction. Among those synthesized, two-thirds of the deoxybenzoins exhibited moderate to good efficacy on relaxing contracted artery including 2,4-dihydroxydeoxybenzoin with EC50=3.30 μM (Emax=100%, n=7) and 2,4-dihydroxy-4'-methoxydeoxybenzoin EC50=3.70 μM (Emax=100%, n=5). Deoxybenzoins displayed an endothelium-dependent relaxing manner on the contracted artery; the contractile responses of neither endothelium denuded nor L-NAME deactivated rings were inhibited. The structure-activity relationships of deoxybenzoin on arterial relaxing effects concluded that the 2,4-dihydroxylated deoxybenzoins presented a potential vascular relaxing pharmacophore, with favoring substitution on ring B in the order of H≥p-OMe>p-OH>o-OMe>m,p-diOMe≥m-OMe.
Lu
Tzy-Ming
TM
Department of Pharmacy, Tajen University, Pingtung 907, Taiwan. cmlu@mail.tajen.edu.tw
Kuo
Daih-Huang
DH
Ko
Horng-Huey
HH
Ng
Lean-Teik
LT
D000818:Animals; D001573:Benzoin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D059808:Polyphenols; D013329:Structure-Activity Relationship; D034421:Sus scrofa; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D014665:Vasodilator Agents; C492807:deoxybenzoin; D001573:Benzoin