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.
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