In vitro antiproliferative activity against human colon cancer cell lines of representative 4-thiazolidinones. Part I

• Published in: Bioorganic & medicinal chemistry letters 2005-09, Vol.15 (17), p.3930-3933
• Main Authors: Ottanà, Rosaria, Carotti, Stefania, Maccari, Rosanna, Landini, Ida, Chiricosta, Giuseppa, Caciagli, Barbara, Vigorita, Maria Gabriella, Mini, Enrico
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative activity; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Cyclooxygenase; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - chemistry; Cyclooxygenase Inhibitors - pharmacology; Drug Screening Assays, Antitumor; General aspects; Human colon cancer; Humans; Inhibitory Concentration 50; Medical sciences; Membrane Proteins; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases - drug effects; Structure-Activity Relationship; Thiazolidinediones - chemistry; Thiazolidinediones - pharmacology; Thiazolidinones
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.05.093

The characterization of two cyclooxygenase isoforms (COX), the rate-limiting enzyme for the synthesis of prostaglandins (PGs) from arachidonic acid, has allowed the development of COX-2 selective inhibitors as non-steroidal anti-inflammatory drugs (NSAIDs) with significant gastric tolerability. However, PGs are also important in cancer pathogenesis. Thus, there is an increasing interest in studying COX-2 inhibitors as potential drugs aimed at the prevention and treatment of cancer, especially colorectal cancer. The purpose of this study was to determine the inhibitory effects of some representative 4-thiazolidinones, already widely investigated as potential NSAIDs, on the growth of five human colon carcinoma cell lines with a different COX-2 expression, and to correlate them with COX-2 inhibitory properties. Our results preliminarily revealed that 2-phenylimino derivative 3 and 2,4-thiazolidindione 4 were the most active compounds. In particular, 3 mainly inhibited the HT29 cell line characterized by a high COX-2 expression, whereas 4 showed antiproliferative properties on all tested cell lines, suggesting molecular targets other than COX-2 inhibition.