Antitumor Activity of New Silylmethyloxyimino Derivatives in vivo and in vitro

Abstract

To investigate the mechanism of action involved in antitumor activity with new silylmethyloxyimino derivatives, antitumor and immunomodulating effects of these derivatives were examined. Selected Trimethylsilylmethyloxyimino cyclohexane (SDK-37) and 2-Dimethylphenylsilylmethyloxyimino butane (SDK-40A) administered i.p. or p.o. were found to be relatively effective on Bl6 melanoma and Ehrlich solid tumors, while ineffective to LI210 and P388 leukemias in vivo. Especially, SDK-37 (400 mg/kg) injected i.p. singly represented significant prolonged life span against Ehrlich ascites carcinoma (EAC). Both SDK-37 and SDK-40A possessed the inhibitory effect of cell growth in various tissue cultured cells in vitro. The IC50 of SDK-40A was 31 yg/ml against EAC, 43 μg/ml against Lewis lung carcinoma, 66 μg/ml against Bl6 melanoma and 47 μg/ml against KB cell. Moreover, SDK-40A inhibited significantly the incorporation of [3H]-labeled precursors into DNA and protein in cultured EAC. We also found that the cell-killing effect of SDK-40A was dependent on both the concentration and time using soft-agar colony assay in KB cells. On the other hand, a significant increase of delayed-type hypersensitivity (DTH) response induced by SDK-37 was seen when SDK-37 was administered i.p. simultanously with immunization of Sheep red blood cell (SRBC) antigen in old aged mice. However, no argumentation of DTH response was induced by SDK-40A in normal ICR-CDl mice.