Design, synthesis, and anti-tumor activity of 4'-thionucleosides as potent and selective agonists at the human A3 adenosine receptor.
On the basis of potent and selective binding affinity of Cl-IB-MECA to the human A(3) adenosine receptor, its 4'-thioadenosine derivatives were efficiently synthesized starting from D-gulonic gamma-lactone. Among compounds tested, 2-chloro-N(6)-(3-iodobenzyl)- and 2-chloro-N(6)-methyl-4' -thioadenosine-5' -methyluronamides (7a and 7b) exhibited nanomolar range of binding affinity (K(i) = 0.38 nM and 0.28 nM, respectively) at the human A(3)AR. These compounds showed anti-growth effects on HL-60 leukemia cell, which resulted from the inhibition of Wnt signaling pathway.
Jeong
Lak Shin
LS
College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea. lakjeong@ewha.ac.kr
Lee
Hyuk Woo
HW
Kim
Hea Ok
HO
Jung
Ji Young
JY
Gunaga
Prashantha
P
Lee
Sang Kook
SK
Lee
Eun-Jin
EJ
Chun
Moon Woo
MW
Gao
Zhan-Guo
ZG
Jacobson
Kenneth A
KA
Moon
Hyung Ryong
HR
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D058909:Adenosine A3 Receptor Agonists; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D018922:HL-60 Cells; D006801:Humans; D013872:Thionucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors
C520185:2-chloro-4'-thioadenosine-5'-methyluronamide; C506205:2-chloro-N(6)-methyladenosine-5'-methyluronamide; D058909:Adenosine A3 Receptor Agonists; D000970:Antineoplastic Agents; D013872:Thionucleosides; D051153:Wnt Proteins; D000241:Adenosine