In vitro activity of novel sulphonic derivatives of distamycin A.
The successful growth of tumors is dependent on the process of vascularization elicited by the tumor itself. As confirmed by many authors, there is a correlation between the presence of factors that stimulate tumor growth and angiogenesis. One of the approaches we have explored to control angiogenesis has been to synthesize compounds able to complex growth factors. A number of sulphonated derivatives of distamycin A were found active in inhibiting the binding of bFGF and PDGF beta on Swiss 3T3 cells with ID50 values ranging between 142-587 microM for bFGF and 28-79 microM for PDGF beta. The effect of these new derivatives in inhibiting angiogenesis was initially explored in the chorioallantoic membrane assay. It was observed that the selected compounds were active in this model system at the concentration of 350 nm/pellet. These new molecules present low or no cytotoxic activity on M5076 murine reticulosarcoma cells, the ID50 values being higher than 60 microM after 72 h continuous exposure in vitro.
Mariani
M
M
Farmitalia Carlo Erba, Erbamont Group, Research and Development Center, Nerviano, Italy.
Paio
A
A
Ciomei
M
M
Pastori
W
W
Franzetti
C
C
Melegaro
G
G
Grandi
M
M
Mongelli
N
N
D016475:3T3 Cells; D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D004214:Distamycins / Q000138:chemical synthesis / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse; D051379:Mice; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004214:Distamycins; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D013451:Sulfonic Acids; D016222:Fibroblast Growth Factor 2; D004317:Doxorubicin; C030000:stallimycin; D017479:Receptors, Platelet-Derived Growth Factor