2-phenylindole-linked nitroimidazoles as potential radiosensitizers for estrogen receptor positive tumors

Abstract

5-Hydroxy-2-(4-hydroxyphenyl)-3-methylindole was linked to nitroimidazoles by tetramethylene and hexamethylene spacer groups. Derivatives with a C₆-spacer (4c and 4d) exhibited high binding affinities for the estrogen receptor (RBA = 3.5; estradiol: 100), a prerequisite for a selective uptake by estrogen receptor positive tumors. Both compounds inhibited the growth of hormone-sensitive human MCF-7 mammary tumor cells at concentrations greater than 5 x 10⁻⁶ M, presumably due to the weak antiestrogenic effect observed in the mouse uterine weight test.