2,4-Bis(octadecanoylamino)benzenesulfonic acid sodium salt as a novel scavenger receptor inhibitor with low molecular weight.
In order to investigate the effect of the fixation of the orientations of the two long chains, three types of novel derivatives of scavenger receptor inhibitor 1 were synthesized, and their biological activities were evaluated. Among the novel derivatives, 2,4-bis(octadecanoylamino)benzenesulfonic acid sodium salt (4d) showed the most potent inhibitory activity against the incorporation of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-labeled acetyl-LDL (DiI-acetyl-LDL) into macrophages. 2,5-Bis(octadecanoylamino)benzenesulfonic acid sodium salt (4c), a regioisomer of 4d, did not exhibit as potent an inhibitory activity as 4d, meaning that the substitution pattern of two long chains on the benzene ring must be important. Compound 4d exhibited 10 times more potent inhibitory activity against the binding of 125I-labeled acetyl-LDL to the surface of macrophages than compound 1.
Yoshiizumi
Kazuya
K
R & D Laboratories, Nippon Organon K.K., 1-5-90, Tomobuchi-cho, Miyakojima-ku, Osaka 534-0016, Japan. zumikazu@kd6.so-net.ne.jp
Nakajima
Fumio
F
Dobashi
Rika
R
Nishimura
Noriyasu
N
Ikeda
Shoji
S
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy; D001557:Benzenesulfonates / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008970:Molecular Weight; D011485:Protein Binding / Q000187:drug effects; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D051116:Receptors, Scavenger; D013329:Structure-Activity Relationship
D001557:Benzenesulfonates; D008077:Lipoproteins, LDL; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C032365:benzenesulfonic acid