Chemistry and anti-tumor activity of sperabillin polymers.
Sperabillin A, 3-[[(3R,5R)-3-amino-6-[(2E,4Z)-2,4-hexadienoylamino]- 5-hydroxyhexanoyl]amino]propanamidine dihydrochloride, was polymerized on standing for several days under a highly humid atmosphere or in the presence of radical initiators. The average molecular weight of the polymers obtained could be regulated by changing the reaction conditions in the latter case. Spectral analyses of the polymers revealed that the 2,4-hexadienoyl moiety of sperabillins was polymerized in a free radical-initiated reaction. The polymers selectively inhibited the proliferation of human umbilical vein endothelial (HUVE) cells. Polymers having higher molecular weight showed stronger inhibition of HUVE cell proliferation. In addition, the polymers showed anti-tumor activity against B16 melanoma in vivo.
Hida
T
T
Discovery Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Tsubotani
S
S
Hori
A
A
Murakami
M
M
Natsugari
H
H
Kozai
Y
Y
Harada
S
S
D000578:Amidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D011108:Polymers / Q000138:chemical synthesis / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000578:Amidines; D000903:Antibiotics, Antineoplastic; D011108:Polymers; C073529:sperabillin A