941839-41-4Relevant academic research and scientific papers
Modulation of carcinogen metabolizing enzymes by new fused heterocycles pendant to 5,6,7,8-tetrahydronaphthalene derivatives
Hamdy, Nehal A.,Gamal-Eldeen, Amira M.,Abdel-Aziz, Hatem A.,Fakhr, Issa M.I.
, p. 463 - 470 (2010)
The treatment of 2-bromo-1-(5,6,7,8-tetrahydro-naphthalen-2-yl)-ethanone (1) with pyridine, 2-methylpyridine or 4-methylpyridine afforded their corresponding pyridinum bromides 3a-c. The latter salts reacted with activated acetylene to give the corresponding indolizine derivatives 6a-c. Imidazo[1,2-a]pyridine 9a,b, quinoxaline 15, imidazo[1,2-b][1,2,4]triazole 18 and imidazo[1,2-a]benzimidazole 21 derivatives were prepared from 1 as a starting material. The investigation of the derivative influence on the carcinogen metabolizing enzymes and in the tumor initiation process revealed that 3a-c were strong inducers of epoxide hydrolase (mEH), and that 3a was an inducer of glutathione S-transferases (GSTs) and glutathione (GSH) and a potent scavenger of ROO{radical dot} and OH{radical dot} and inhibited the induced DNA damage, while 3b was a scavenger of ROO{radical dot} and a moderate inhibitor of DNA damage. Additionally, 6a-c significantly induced quinine reductase (QR) activity, whereas 6b induced GSTs, and 6c elevated GSH content, while both of 6b and 6c scavenged OH{radical dot} and inhibited the DNA damage. On the other hand, 9a possessed a moderate scavenging activity of ROO{radical dot} and inhibitory effect on the induced DNA damage, while 18 was a strong inducer of QR activity, scavenger of OH{radical dot}, and inhibitor of the DNA damage and 2 was a significant inhibitor of cytochrome P-450 1A (Cyp1A) and was an inducer of GSTs, and GSH, and a moderate inhibitor of the DNA damage.
