Synthesis and biological activity of spergualin analogues. I.
Stable spergualin analogues were synthesized by substitutions of the alpha-hydroxyglycine residue of spergualin with various alpha- or omega-amino acids. The antitumor activity of these analogues against L1210 and their immunosuppressive effects on delayed-type hypersensitivity and antibody formation was then examined. Analogues substituted with glycine and L-serine showed significant biological activity but were less potent than 15-deoxyspergualin. Among the analogues synthesized so far, 10-[N-4-(4-guanidinophenyl)butyryl-L-seryl]-1,5,10-triazadecane has possessed the strongest antitumor and immunosuppressive activities.
Nishizawa
R
R
Research Laboratories, Nippon Kayaku Co., Ltd., Tokyo, Japan.
Takei
Y
Y
Yoshida
M
M
Tomiyoshi
T
T
Saino
T
T
Nishikawa
K
K
Nemoto
K
K
Takahashi
K
K
Fujii
A
A
Nakamura
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology; D006146:Guanidines / Q000138:chemical synthesis / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D006146:Guanidines; D007166:Immunosuppressive Agents; C033797:spergualin