Delaminomycins, novel extracellular matrix receptor antagonist. IV. Structure-activity relationships of delaminomycins and derivatives.
Delaminomycins A, B, C and their derivatives were prepared and investigated biological activities of them. Among these compounds, spiro compounds (A2, B2 and C2) showed stronger inhibitory activity than natural products (A1, B1 and C1) on B16 melanoma cells adhesion assay and Con A-induced proliferation of murine splenic lymphocytes assay. In MLCR and antimicrobial assay, however, A1, B1 and C1 showed more potent inhibitory activity than spiro compounds (A2, B2 and C2). On the other hand, as to C-5' substituents of pyrrolidine ring, the order of inhibitory activity was R = OH > R = OCH3 > R = H on Con A-induced proliferation of murine splenic lymphocytes assay. In MLCR and antimicrobial assay, however, the order of inhibitory activities were R = H > R = OCH3 > R = OH. Inhibitory activities of A4 which was lacked pyrrolidine ring were reduced on B16 melanoma cells adhesion assay and on cytotoxicity against tumor cells in vitro in comparison with those of A1.
Ueno
M
M
Institute for Chemotherapy, Microbial Chemistry Research Foundation, Shizuoka, Japan.
Amemiya
M
M
Yamazaki
K
K
Iijima
M
M
Osono
M
M
Someno
T
T
Iinuma
H
H
Hamada
M
M
Ishizuka
M
M
Takeuchi
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008826:Microbial Sensitivity Tests; D011760:Pyrrolidinones / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D011760:Pyrrolidinones; D013764:Tetrahydronaphthalenes; C082438:delaminomycin A; C082440:delaminomycin B; C082441:delaminomycin C