Synthesis and biological evaluation of new tri-heterocyclic derivatives as anti-colorectal cancer agents
Colorectal cancer is a major health problem, with a poor prognosis if not detected at early stage. It is the third most common cancer worldwide and the second most deadly. Thus, discovering new treatments became an absolute priority for many research laboratories to improve the prognosis. The involv...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715624007112 |
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| author | Benjamin Victoir Océane Pertegaz Elfi Ducrocq Marion Polomski Maxime Guéguinou William Raoul Cécile Croix Gildas Prié |
| author_facet | Benjamin Victoir Océane Pertegaz Elfi Ducrocq Marion Polomski Maxime Guéguinou William Raoul Cécile Croix Gildas Prié |
| author_sort | Benjamin Victoir |
| collection | DOAJ |
| description | Colorectal cancer is a major health problem, with a poor prognosis if not detected at early stage. It is the third most common cancer worldwide and the second most deadly. Thus, discovering new treatments became an absolute priority for many research laboratories to improve the prognosis. The involvement of STAT3/5 in the development of colorectal cancer is well established and has led to the development of new inhibitors of these proteins. This work was guided by the previous identification of a potent STAT5 inhibitor in the fight against myeloid leukemias. Pharmacomodulations were strategically performed, and the in vitro activities of all tri-heterocyclic derivatives were assessed on HT29 and Lovo colorectal cancer cell lines, as well as on the non-tumoral NCM356 colonic epithelial cell line derived from normal mucosa. Compared with 5-fluorouracil classically used in the treatment strategy for colorectal cancer patients, some of our compounds showed better activity on cancer cells. In particular, compound 1b blocked the growth of colorectal cancer cells at sub-micromolar concentrations, thus represents a promising lead compound in the fight against colorectal cancer. |
| format | Article |
| id | doaj-art-8cd4939baa13405191bdd739564f9837 |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-8cd4939baa13405191bdd739564f98372025-01-29T05:00:56ZengElsevierResults in Chemistry2211-71562025-01-0113102015Synthesis and biological evaluation of new tri-heterocyclic derivatives as anti-colorectal cancer agentsBenjamin Victoir0Océane Pertegaz1Elfi Ducrocq2Marion Polomski3Maxime Guéguinou4William Raoul5Cécile Croix6Gildas Prié7INSERM UMR 1100 CEPR, Equipe “Mécanismes Protéolytiques Dans L’inflammation”, Faculté de Médecine, 10 Boulevard Tonnellé, BP 3223, 37032 Tours Cedex 01, FranceINSERM UMR 1069 N2COx « Niche, Nutrition, Cancer et métabolisme Oxydatif », Faculté de Médecine, 10 Boulevard Tonnellé, BP 3223, 37032 Tours Cedex 01, FranceINSERM UMR 1069 N2COx « Niche, Nutrition, Cancer et métabolisme Oxydatif », Faculté de Médecine, 10 Boulevard Tonnellé, BP 3223, 37032 Tours Cedex 01, FranceINSERM UMR 1100 CEPR, Equipe “Mécanismes Protéolytiques Dans L’inflammation”, Faculté de Médecine, 10 Boulevard Tonnellé, BP 3223, 37032 Tours Cedex 01, FranceINSERM UMR 1069 N2COx « Niche, Nutrition, Cancer et métabolisme Oxydatif », Faculté de Médecine, 10 Boulevard Tonnellé, BP 3223, 37032 Tours Cedex 01, FranceINSERM UMR 1069 N2COx « Niche, Nutrition, Cancer et métabolisme Oxydatif », Faculté de Médecine, 10 Boulevard Tonnellé, BP 3223, 37032 Tours Cedex 01, FranceINSERM UMR 1100 CEPR, Equipe “Mécanismes Protéolytiques Dans L’inflammation”, Faculté de Médecine, 10 Boulevard Tonnellé, BP 3223, 37032 Tours Cedex 01, FranceINSERM UMR 1100 CEPR, Equipe “Mécanismes Protéolytiques Dans L’inflammation”, Faculté de Médecine, 10 Boulevard Tonnellé, BP 3223, 37032 Tours Cedex 01, France; Corresponding author.Colorectal cancer is a major health problem, with a poor prognosis if not detected at early stage. It is the third most common cancer worldwide and the second most deadly. Thus, discovering new treatments became an absolute priority for many research laboratories to improve the prognosis. The involvement of STAT3/5 in the development of colorectal cancer is well established and has led to the development of new inhibitors of these proteins. This work was guided by the previous identification of a potent STAT5 inhibitor in the fight against myeloid leukemias. Pharmacomodulations were strategically performed, and the in vitro activities of all tri-heterocyclic derivatives were assessed on HT29 and Lovo colorectal cancer cell lines, as well as on the non-tumoral NCM356 colonic epithelial cell line derived from normal mucosa. Compared with 5-fluorouracil classically used in the treatment strategy for colorectal cancer patients, some of our compounds showed better activity on cancer cells. In particular, compound 1b blocked the growth of colorectal cancer cells at sub-micromolar concentrations, thus represents a promising lead compound in the fight against colorectal cancer.http://www.sciencedirect.com/science/article/pii/S2211715624007112Colorectal cancerSTAT5 inhibitorHeterocyclic compoundsTetrahydroquinolinePyrimidine corePharmacomodulation |
| spellingShingle | Benjamin Victoir Océane Pertegaz Elfi Ducrocq Marion Polomski Maxime Guéguinou William Raoul Cécile Croix Gildas Prié Synthesis and biological evaluation of new tri-heterocyclic derivatives as anti-colorectal cancer agents Results in Chemistry Colorectal cancer STAT5 inhibitor Heterocyclic compounds Tetrahydroquinoline Pyrimidine core Pharmacomodulation |
| title | Synthesis and biological evaluation of new tri-heterocyclic derivatives as anti-colorectal cancer agents |
| title_full | Synthesis and biological evaluation of new tri-heterocyclic derivatives as anti-colorectal cancer agents |
| title_fullStr | Synthesis and biological evaluation of new tri-heterocyclic derivatives as anti-colorectal cancer agents |
| title_full_unstemmed | Synthesis and biological evaluation of new tri-heterocyclic derivatives as anti-colorectal cancer agents |
| title_short | Synthesis and biological evaluation of new tri-heterocyclic derivatives as anti-colorectal cancer agents |
| title_sort | synthesis and biological evaluation of new tri heterocyclic derivatives as anti colorectal cancer agents |
| topic | Colorectal cancer STAT5 inhibitor Heterocyclic compounds Tetrahydroquinoline Pyrimidine core Pharmacomodulation |
| url | http://www.sciencedirect.com/science/article/pii/S2211715624007112 |
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