In vitro antiproliferative activity against human colon cancer cell lines of representative 4-thiazolidinones. Part I
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. Howe...
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Published in | Bioorganic & medicinal chemistry letters Vol. 15; no. 17; pp. 3930 - 3933 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Elsevier Ltd
01.09.2005
Elsevier |
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Abstract | 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. |
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AbstractList | 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. 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. |
Author | Maccari, Rosanna Carotti, Stefania Caciagli, Barbara Vigorita, Maria Gabriella Ottanà, Rosaria Landini, Ida Chiricosta, Giuseppa Mini, Enrico |
Author_xml | – sequence: 1 givenname: Rosaria surname: Ottanà fullname: Ottanà, Rosaria organization: Dipartimento Farmaco-chimico, Università di Messina,Viale SS. Annunziata, 98168 Messina, Italy – sequence: 2 givenname: Stefania surname: Carotti fullname: Carotti, Stefania organization: Dipartimento di Farmacologia Preclinica e Clinica, Università di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy – sequence: 3 givenname: Rosanna surname: Maccari fullname: Maccari, Rosanna organization: Dipartimento Farmaco-chimico, Università di Messina,Viale SS. Annunziata, 98168 Messina, Italy – sequence: 4 givenname: Ida surname: Landini fullname: Landini, Ida organization: Dipartimento di Farmacologia Preclinica e Clinica, Università di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy – sequence: 5 givenname: Giuseppa surname: Chiricosta fullname: Chiricosta, Giuseppa organization: Dipartimento Farmaco-chimico, Università di Messina,Viale SS. Annunziata, 98168 Messina, Italy – sequence: 6 givenname: Barbara surname: Caciagli fullname: Caciagli, Barbara organization: Dipartimento di Farmacologia Preclinica e Clinica, Università di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy – sequence: 7 givenname: Maria Gabriella surname: Vigorita fullname: Vigorita, Maria Gabriella email: vigorita@pharma.unime.it organization: Dipartimento Farmaco-chimico, Università di Messina,Viale SS. Annunziata, 98168 Messina, Italy – sequence: 8 givenname: Enrico surname: Mini fullname: Mini, Enrico organization: Dipartimento di Farmacologia Preclinica e Clinica, Università di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy |
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Keywords | Human colon cancer Cyclooxygenase Thiazolidinones Antiproliferative activity Antineoplastic agent Prostaglandin-endoperoxide synthase Carcinoma Growth Cyclooxygenase 2 Colorectal cancer Cyclooxygenase 2 inhibitor Selectivity Colon cancer Intestinal disease Colon Chemical synthesis Tumor cell Human Enzyme Enzyme inhibitor Malignant tumor In vitro Biological activity Cell line Digestive diseases Oxidoreductases |
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SubjectTerms | 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 |
Title | In vitro antiproliferative activity against human colon cancer cell lines of representative 4-thiazolidinones. Part I |
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