Perrella F W, Chen S F, Behrens D L, Kaltenbach R F, Seitz S P
Cancer Research Group, DuPont Merck Pharmaceutical Company, Glenolden Laboratory, Pennsylvania 19036.
J Med Chem. 1994 Jul 8;37(14):2232-7. doi: 10.1021/jm00040a016.
A series of nitrocoumarin and nitrochromene derivatives have been prepared and shown to inhibit the phosphatidylinositol-specific phospholipase C(PLC)(IC50 < 10 micrograms/mL) isolated from human melanoma. The inhibition of PLC by nitrocoumarin 4a was time-dependent and irreversible. The inhibition of PLC was shown to interfere with inositide metabolism in whole cells (IC50 = 4 micrograms/mL) in a manner consistent with their proposed mode of activity. Finally, the compounds were shown to be growth inhibitory to cultured melanoma cells (ID50 = 2 micrograms/mL), suggesting that PLC may be an attractive new target for chemotherapeutic intervention.
已制备出一系列硝基香豆素和硝基色烯衍生物，它们能够抑制从人黑色素瘤中分离出的磷脂酰肌醇特异性磷脂酶C（PLC）（IC50 < 10微克/毫升）。硝基香豆素4a对PLC的抑制作用具有时间依赖性且不可逆。研究表明，对PLC的抑制会干扰全细胞中的肌醇磷脂代谢（IC50 = 4微克/毫升），其方式与所提出的活性模式一致。最后，这些化合物对培养的黑色素瘤细胞具有生长抑制作用（ID50 = 2微克/毫升），这表明PLC可能是化疗干预的一个有吸引力的新靶点。
