Evaluation of anticancer activity of 4-vinyl-1-arylsulfonylimidazolidinones.
To continue exploration of structure activity relationship of novel 1-(indoline-5-sulfonyl)-4-phenylimidazolidinones (1) reported as anticancer agent with broad spectrum, three 1-(arylsulfonyl)-4-vinylimidazolidinones (2) were synthesized from methyl serinate (3) in 8 steps. Reaction of intermediate 2-phenoxycarbonylaminobut-3-enyl p-toluenesulfonate (10) with arylsulfonamide in the presence of potassium carbonate produced corresponding 2 and N-(4-vinyloxazolidin-2-yl)arylsulfonamide 11 in approximately equal ratio. This reaction is believed to undergo through urea intermediate 16 as shown in scheme 3. 1-Arylsufonyl-4-vinylimidazolidinones 2 show much reduced activity against human colon carcinoma (Colo205), human chronic myelogenous leukemia (K562), and human ovarian adenocarcinoma (SK-OV-3) and compatible activity against human lung carcinoma (A549) compared to 1. Therefore phenyl at 4-position should be the optimum planar motif for the activity of 1.
Kwak
Son-Hyok
SH
College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea.
Bang
Seong-Cheol
SC
Seo
Hyun-Hee
HH
Shin
Hye-Rim
HR
Lee
Ki-Cheul
KC
Le Hoang
Tuan Anh
TA
Jung
Sang-Hun
SH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006827:Hydantoins / Q000138:chemical synthesis* / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D006827:Hydantoins; D013778:Tetrazolium Salts; D013844:Thiazoles; D014753:Vinyl Compounds; C022616:thiazolyl blue