Umbelliferone analogues and their potential to inhibit Benzo(a)pyrene- and hydrogen peroxide-induced mutations.
Following the natural product lead, farneciferol-D (kopetdaghin, 8), some ether analogues of umbelliferone were synthesized and assayed for their potential to be antimutagenic/anticarcinogenic against mutations induced by benzo(a)pyrene, a potent mutagen/carcinogen, and hydrogen peroxide, and for their ability to function as free radical scavengers. The "true" antimutagenic effect of these compounds was determined at half the nontoxic concentration in Salmonella typhimurium strains utilizing a modified Ames test protocol, and their free radical-scavenging ability was assayed utilizing a nonenzymatic phenazine methosulfate (PMS)-NADH system. Umbelliferone analogues 4 and 5 demonstrated good potential in preventing mutations induced by benzo(a)pyrene and hydrogen peroxide and also exhibited good superoxide scavenging ability in the PMS-NADH assay, suggesting that the antimutagenic activity of these analogues may be linked to their antioxidative properties.
Pillai
S P
SP
Departments of Medicinal Chemistry and Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, USA.
Menon
S R
SR
Mitscher
L A
LA
Pillai
C A
CA
Shankel
D M
DM
D016587:Antimutagenic Agents / Q000737:chemistry / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009154:Mutation; D012486:Salmonella typhimurium / Q000235:genetics; D013481:Superoxides / Q000737:chemistry; D014468:Umbelliferones / Q000737:chemistry / Q000494:pharmacology*
D016587:Antimutagenic Agents; D016166:Free Radical Scavengers; D014468:Umbelliferones; D013481:Superoxides; D001564:Benzo(a)pyrene; C031477:7-hydroxycoumarin; D006861:Hydrogen Peroxide