The antitumor activities of novel 1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenyl-imidazolidin-2-ones were studied to determine the potential of these compounds as antitumor candidates. The agents studied were: DW2143 (1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenyl-imidazolidin-2-one), a racemic mixture, and
DW2282 [(4S)-1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenyl-imidazolidin-2-one], an S-isomer. DW2143 and
DW2282 suppressed the in vitro growth of
tumor cells at lower concentrations than
doxorubicin, but
tumor specificity was not observed between the compounds. These compounds when administered orally were not active in syngeneic models of murine Colon 26
adenocarcinoma and
L1210 leukemia. However, DW2143 suppressed the growth of SW620 (human
colon cancer) and NCI-H23 (human
lung cancer) cells in nude mice, inhibiting
tumor growth by 87 and 67%, respectively.
DW2282 was a more potent inhibitor of SW620
tumor cell growth in nude mice and was also lower in toxicity than DW2143. Moreover,
DW2282 did not produce a series of toxic symptoms caused by the
aniline metabolites of sulfonylureas, including
hypoglycemia. These results suggest that
DW2282, an S-isomer, could be a novel antitumor candidate with higher specificity and lower toxicity than other orally active sulfonylureas.