4,5-Diaryl 3(<em>2H</em>)Furanones: Anti-Inflammatory Activity and Influence on Cancer Growth
Apart from their anti-inflammatory action, COX inhibitors have gathered the interest of many scientists due to their potential use for the treatment and prevention of cancer. It has been shown that cyclooxygenase inhibitors restrict cancer cell growth and are able to interact with known antitumor dr...
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MDPI AG
2019-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/9/1751 |
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| author | Dmitrii Semenok Jury Medvedev Lefki-P. Giassafaki Iason Lavdas Ioannis S. Vizirianakis Phaedra Eleftheriou Antonis Gavalas Anthi Petrou Athina Geronikaki |
| author_facet | Dmitrii Semenok Jury Medvedev Lefki-P. Giassafaki Iason Lavdas Ioannis S. Vizirianakis Phaedra Eleftheriou Antonis Gavalas Anthi Petrou Athina Geronikaki |
| author_sort | Dmitrii Semenok |
| collection | DOAJ |
| description | Apart from their anti-inflammatory action, COX inhibitors have gathered the interest of many scientists due to their potential use for the treatment and prevention of cancer. It has been shown that cyclooxygenase inhibitors restrict cancer cell growth and are able to interact with known antitumor drugs, enhancing their in vitro and in vivo cytotoxicity. The permutation of hydrophilic and hydrophobic aryl groups in COX inhibitors leads to cardinal changes in the biological activity of the compounds. In the present study, thirteen heterocyclic coxib-like 4,5-diarylfuran-3(<i>2H</i>)-ones and their annelated derivatives—phenanthro[9,10-b]furan-3-ones—were synthesized and studied for anti-inflammatory and COX-1/2 inhibitory action and for their cytotoxic activity on the breast cancer (MCF-7) and squamous cell carcinoma (HSC-3) cell lines. The F-derivative of the –SOMe substituted furan-3(<i>2H</i>)-ones exhibited the best activity (COX-1 IC<sub>50</sub> = 2.8 μM, anti-inflammatory activity (by carrageenan paw edema model) of 54% (dose 0.01 mmol/kg), and MCF-7 and HSC-3 cytotoxicity with IC<sub>50</sub> values of 10 μM and 7.5 μM, respectively). A cytotoxic effect related to the COX-1 inhibitory action was observed and a synergistic effect with the anti-neoplastic drugs gefitinib and 5-fluorouracil was found. A phenanthrene derivative exhibited the best synergistic effect with gefitinib. |
| first_indexed | 2024-12-11T19:07:51Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T19:07:51Z |
| publishDate | 2019-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-876546646ee2448a866f3c25d196c42f2022-12-22T00:53:51ZengMDPI AGMolecules1420-30492019-05-01249175110.3390/molecules24091751molecules240917514,5-Diaryl 3(<em>2H</em>)Furanones: Anti-Inflammatory Activity and Influence on Cancer GrowthDmitrii Semenok0Jury Medvedev1Lefki-P. Giassafaki2Iason Lavdas3Ioannis S. Vizirianakis4Phaedra Eleftheriou5Antonis Gavalas6Anthi Petrou7Athina Geronikaki8Skolkovo Institute of Science and Technology, Skolkovo Innovation Center, 3 Nobel Street, 143026 Moscow, RussiaSaint-Petersburg State University, Institute of Chemistry, Universitetskiy Prospekt, 26, 198504 Petergof, RussiaDepartment of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Medical Laboratory Studies, School of Health and Medical Care, Alexander Technological Educational Institute of Thessaloniki, 57400 Thessaloniki, GreeceDepartment of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceApart from their anti-inflammatory action, COX inhibitors have gathered the interest of many scientists due to their potential use for the treatment and prevention of cancer. It has been shown that cyclooxygenase inhibitors restrict cancer cell growth and are able to interact with known antitumor drugs, enhancing their in vitro and in vivo cytotoxicity. The permutation of hydrophilic and hydrophobic aryl groups in COX inhibitors leads to cardinal changes in the biological activity of the compounds. In the present study, thirteen heterocyclic coxib-like 4,5-diarylfuran-3(<i>2H</i>)-ones and their annelated derivatives—phenanthro[9,10-b]furan-3-ones—were synthesized and studied for anti-inflammatory and COX-1/2 inhibitory action and for their cytotoxic activity on the breast cancer (MCF-7) and squamous cell carcinoma (HSC-3) cell lines. The F-derivative of the –SOMe substituted furan-3(<i>2H</i>)-ones exhibited the best activity (COX-1 IC<sub>50</sub> = 2.8 μM, anti-inflammatory activity (by carrageenan paw edema model) of 54% (dose 0.01 mmol/kg), and MCF-7 and HSC-3 cytotoxicity with IC<sub>50</sub> values of 10 μM and 7.5 μM, respectively). A cytotoxic effect related to the COX-1 inhibitory action was observed and a synergistic effect with the anti-neoplastic drugs gefitinib and 5-fluorouracil was found. A phenanthrene derivative exhibited the best synergistic effect with gefitinib.https://www.mdpi.com/1420-3049/24/9/17513(<i>2H</i>)furanonesphenanthro[9,10-b]furanonescyclooxygenasecytotoxicityanticancerMCF-7HSC-3gefitinib5-fluorouracil |
| spellingShingle | Dmitrii Semenok Jury Medvedev Lefki-P. Giassafaki Iason Lavdas Ioannis S. Vizirianakis Phaedra Eleftheriou Antonis Gavalas Anthi Petrou Athina Geronikaki 4,5-Diaryl 3(<em>2H</em>)Furanones: Anti-Inflammatory Activity and Influence on Cancer Growth Molecules 3(<i>2H</i>)furanones phenanthro[9,10-b]furanones cyclooxygenase cytotoxicity anticancer MCF-7 HSC-3 gefitinib 5-fluorouracil |
| title | 4,5-Diaryl 3(<em>2H</em>)Furanones: Anti-Inflammatory Activity and Influence on Cancer Growth |
| title_full | 4,5-Diaryl 3(<em>2H</em>)Furanones: Anti-Inflammatory Activity and Influence on Cancer Growth |
| title_fullStr | 4,5-Diaryl 3(<em>2H</em>)Furanones: Anti-Inflammatory Activity and Influence on Cancer Growth |
| title_full_unstemmed | 4,5-Diaryl 3(<em>2H</em>)Furanones: Anti-Inflammatory Activity and Influence on Cancer Growth |
| title_short | 4,5-Diaryl 3(<em>2H</em>)Furanones: Anti-Inflammatory Activity and Influence on Cancer Growth |
| title_sort | 4 5 diaryl 3 em 2h em furanones anti inflammatory activity and influence on cancer growth |
| topic | 3(<i>2H</i>)furanones phenanthro[9,10-b]furanones cyclooxygenase cytotoxicity anticancer MCF-7 HSC-3 gefitinib 5-fluorouracil |
| url | https://www.mdpi.com/1420-3049/24/9/1751 |
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