• Applied Biological Chemistry
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• v.42 no.1
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• pp.68-72
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• 1999

The cytotoxicity of 1,3-diphenylpropenone derivatives known to inhibit the farnesyl protein transferase (FPTase) was examined against various established tumor cell line, A549 (lung cancer), SKMEL-2 (uterine cancer), HCT-15 (skin cancer), SKOV-3 (brain cancer) and XF-498 (colon cancer) of the 1,3-diphenylpropenone derivatives showing farnesyl protein transferase (FPTase) inhibition activity. And the structure-activity relationship (SAR) between structure of 1,3-diphenylpropenone derivatives as substrate and cytotoxicity was investigated by Free-Wilson analysis as well as Hansch method with tumor cell lines. From the result of Free-Wilson analyses, X-substituents on the benzoyl group have a more important role than Y-substituents on the styryl group. The 2,4-dichloro substituent, 15 and 2,4-dimethyl substituent, 16 showed the highest cytotoxicity (average pI_(50)=5.0). Particulary, the cytotoxicity of X-substituents increased with electronic effect $({\sigma})$ due to weak electron withdrawing group with optimum value $({\sigma}_{opt}=0.22{\sim}0.29})$ whereas that of Y-substituent resulted from various factors such as logP, $B_1$ and R constant.