Synthesis of 3-alkylthio-6-allylthiopyridazine derivatives and their antihepatocarcinoma activity.
The allylthio group of allicin and other organosulfur compounds, isolated from garlic, is considered a pharmacophore, and a key structure component of the molecule, which affords biological activities. In the foregoing studies, various 3-alkoxy-6-allylthiopyridazine derivatives (K-compounds) were synthesized, and their biological activities tested in animals. As expected, the various derivatives showed good hepatoprotective activities on carbon tetrachloride-treated mice and aflatoxin B1-treated rats, and chemopreventive activities on hepatocarcinoma cells in rats. Other new pyridazine derivatives, with the oxygen atom at the 3-position of the 3-alkoxy-6-allylthiopyridazine displaced by sulfur (S), were synthesized, and their activities tested in vitro. Thio-K6, one of the sulfur-substituted compounds, showed better chemopreventive activity toward hepatocarcinoma cells.
Kwon
Soon-Kyoung
SK
College of Pharmacy, Duksung Women's University, Seoul 132-714, Korea. skkwon@duksung.ac.kr
Moon
Aree
A
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013441:Sulfinic Acids / Q000737:chemistry*
D000970:Antineoplastic Agents; D004220:Disulfides; D011724:Pyridazines; D013441:Sulfinic Acids; C006452:allicin