Synthesis of 5'-substituted fluoro-neplanocin A analogues: importance of a hydrogen bonding donor at 5'-position for the inhibitory activity of S-adenosylhomocysteine hydrolase.
Four 5'-substituted fluoro-neplanocin A analogues 1a-d were designed and synthesized, using cyclopentenone derivative 2 as a key intermediate. The inhibitory activity against SAH was in the following order: NH(2)>SH>F, N(3), indicating a hydrogen bonding donor such as OH or NH(2) was essential for inhibitory activity. All the final compounds showed much less decreased cytotoxicity in two cancer cell lines (Col2 and A549), implying that phosphorylation of the 5'-hydroxyl group of fluoro-neplanocin A is closely related to its high cytotoxicity.
College of Pharmacy, Pusan National University, Pusan 609-753, Korea.
Hyung Ryong
HR
Moon
Hyun Joo
HJ
Lee
Kyung Ran
KR
Kim
Kang Man
KM
Lee
Sang Kook
SK
Lee
Hea Ok
HO
Kim
Moon Woo
MW
Chun
Lak Shin
LS
Jeong
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding; D015394:Molecular Structure; D013329:Structure-Activity Relationship
C031096:neplanocin A; D043383:Adenosylhomocysteinase; D000241:Adenosine