Synthesis and Antiproliferative Evaluation of 2′‐Arenesulfonyloxy‐5‐benzylidene‐thiazolidine‐2,4‐diones |
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| Authors: | Emily M. Chen Pei‐Jung Lu Arthur Y. Shaw |
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| Affiliation: | 1. Department of Chemistry, Tamkang University, Danshui 251, Taiwan;2. Institute of Clinical Medicine, National Cheng Kung University, Tainan 701, Taiwan;3. Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona 85721;4. The Southwest Comprehensive Center for Drug Discovery and Development, 1580 E. Hanley Blvd., Oro Valley, Arizona 85737 |
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| Abstract: | A series of 2′‐arenesulfonyloxy‐5‐benzylidene‐thiazolidine‐2,4‐diones (TZDs) were synthesized and examined for their antiproliferative effects on a panel of carcinoma cell lines. Our results indicated that initial synthesis of 5‐[2′‐hydroxybenzylidene]‐2,4‐thiazolidinone (9) by Knoevenagel condensation followed by nucleophilic substitution with arylsulfonyl chlorides exhibited superior efficiency to the alternative synthetic route. Among tested compounds, only 8c and 8e showed significant antiproliferative activity against PC‐3 and BT474 cells with GI50 values of 8.4 and 20.6 μM, respectively. SKHep cells displayed interesting structure‐activity relationships in response to TZD derivatives treatment. Alkyl group‐substituted TZD analogs such as 8a (4‐Me, GI50, 9.4 μM) and 8k (4‐iso‐propyl, GI50, 9.8 μM) revealed better antiproliferative activity than those with bulkier alkyl groups. On the other hand, halogen‐substituted TZD analogs 8c, 8h, and 8i showed better antiproliferative activity against H460 cell line. Together, the new synthesized TZD derivatives 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h , 8i , 8j , 8k , 8l , 8m , 8n , 8o , 8p exhibited appreciable antiproliferative activity worth for further study. |
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