A novel stereo-selective sulfonylurea, 1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenyl-imidazolidin-2-one, has antitumor efficacy in in vitro and in vivo tumor models.
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.
Lee
Chang Woo
CW
Biopotency Evaluation Laboratory, Korea Research Institute of Bioscience and Biotechnology, 305-333, Taejon, South Korea.
Hong
Dong Ho
DH
Han
Sang Bae
SB
Jung
Sang-Hun
SH
Kim
Hyung Chin
HC
Fine
Robert L
RL
Lee
Sang-Han
SH
Kim
Hwan Mook
HM
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008968:Molecular Conformation; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D013450:Sulfones / Q000494:pharmacology; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D007093:Imidazoles; D013450:Sulfones; C404303:DW 2282; C116727:DW 2143