Enriching the Arsenal of Pharmacological Tools against MICAL2
Molecule interacting with CasL 2 (MICAL2), a cytoskeleton dynamics regulator, are strongly expressed in several human cancer types, especially at the invasive front, in metastasizing cancer cells and in the neo-angiogenic vasculature. Although a plethora of data exist and stress a growing relevance...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/24/7519 |
| _version_ | 1827670892132433920 |
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| author | Ivana Barravecchia Elisabetta Barresi Camilla Russo Francesca Scebba Chiara De Cesari Valerio Mignucci Davide De Luca Silvia Salerno Valeria La Pietra Mariateresa Giustiniano Sveva Pelliccia Diego Brancaccio Greta Donati Federico Da Settimo Sabrina Taliani Debora Angeloni Luciana Marinelli |
| author_facet | Ivana Barravecchia Elisabetta Barresi Camilla Russo Francesca Scebba Chiara De Cesari Valerio Mignucci Davide De Luca Silvia Salerno Valeria La Pietra Mariateresa Giustiniano Sveva Pelliccia Diego Brancaccio Greta Donati Federico Da Settimo Sabrina Taliani Debora Angeloni Luciana Marinelli |
| author_sort | Ivana Barravecchia |
| collection | DOAJ |
| description | Molecule interacting with CasL 2 (MICAL2), a cytoskeleton dynamics regulator, are strongly expressed in several human cancer types, especially at the invasive front, in metastasizing cancer cells and in the neo-angiogenic vasculature. Although a plethora of data exist and stress a growing relevance of MICAL2 to human cancer, it is worth noting that only one small-molecule inhibitor, named CCG-1423 (1), is known to date. Herein, with the aim to develop novel MICAL2 inhibitors, starting from CCG-1423 (1), a small library of new compounds was synthetized and biologically evaluated on human dermal microvascular endothelial cells (HMEC-1) and on renal cell adenocarcinoma (786-O) cells. Among the novel compounds, <b>10</b> and <b>7</b> gave interesting results in terms of reduction in cell proliferation and/or motility, whereas no effects were observed in MICAL2-knocked down cells. Aside from the interesting biological activities, this work provides the first structure–activity relationships (SARs) of CCG-1423 (1), thus providing precious information for the discovery of new MICAL2 inhibitors. |
| first_indexed | 2024-03-10T03:29:25Z |
| format | Article |
| id | doaj.art-8dae666ae0a641799df6e215c072523e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T03:29:25Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8dae666ae0a641799df6e215c072523e2023-11-23T09:45:19ZengMDPI AGMolecules1420-30492021-12-012624751910.3390/molecules26247519Enriching the Arsenal of Pharmacological Tools against MICAL2Ivana Barravecchia0Elisabetta Barresi1Camilla Russo2Francesca Scebba3Chiara De Cesari4Valerio Mignucci5Davide De Luca6Silvia Salerno7Valeria La Pietra8Mariateresa Giustiniano9Sveva Pelliccia10Diego Brancaccio11Greta Donati12Federico Da Settimo13Sabrina Taliani14Debora Angeloni15Luciana Marinelli16Institute of Life Sciences, Scuola Superiore Sant’Anna, Via G. Moruzzi 1, 56124 Pisa, ItalyDepartment of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, ItalyDipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Naples, ItalyInstitute of Life Sciences, Scuola Superiore Sant’Anna, Via G. Moruzzi 1, 56124 Pisa, ItalyInstitute of Life Sciences, Scuola Superiore Sant’Anna, Via G. Moruzzi 1, 56124 Pisa, ItalyInstitute of Life Sciences, Scuola Superiore Sant’Anna, Via G. Moruzzi 1, 56124 Pisa, ItalyInstitute of Life Sciences, Scuola Superiore Sant’Anna, Via G. Moruzzi 1, 56124 Pisa, ItalyDepartment of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, ItalyDipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Naples, ItalyDipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Naples, ItalyDipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Naples, ItalyDipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Naples, ItalyDipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Naples, ItalyDepartment of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, ItalyInstitute of Life Sciences, Scuola Superiore Sant’Anna, Via G. Moruzzi 1, 56124 Pisa, ItalyDipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Naples, ItalyMolecule interacting with CasL 2 (MICAL2), a cytoskeleton dynamics regulator, are strongly expressed in several human cancer types, especially at the invasive front, in metastasizing cancer cells and in the neo-angiogenic vasculature. Although a plethora of data exist and stress a growing relevance of MICAL2 to human cancer, it is worth noting that only one small-molecule inhibitor, named CCG-1423 (1), is known to date. Herein, with the aim to develop novel MICAL2 inhibitors, starting from CCG-1423 (1), a small library of new compounds was synthetized and biologically evaluated on human dermal microvascular endothelial cells (HMEC-1) and on renal cell adenocarcinoma (786-O) cells. Among the novel compounds, <b>10</b> and <b>7</b> gave interesting results in terms of reduction in cell proliferation and/or motility, whereas no effects were observed in MICAL2-knocked down cells. Aside from the interesting biological activities, this work provides the first structure–activity relationships (SARs) of CCG-1423 (1), thus providing precious information for the discovery of new MICAL2 inhibitors.https://www.mdpi.com/1420-3049/26/24/7519MICAL2wound healing assayHMEC-1 endothelial cells786-O kidney cancer cellsCCG-1423metastasis |
| spellingShingle | Ivana Barravecchia Elisabetta Barresi Camilla Russo Francesca Scebba Chiara De Cesari Valerio Mignucci Davide De Luca Silvia Salerno Valeria La Pietra Mariateresa Giustiniano Sveva Pelliccia Diego Brancaccio Greta Donati Federico Da Settimo Sabrina Taliani Debora Angeloni Luciana Marinelli Enriching the Arsenal of Pharmacological Tools against MICAL2 Molecules MICAL2 wound healing assay HMEC-1 endothelial cells 786-O kidney cancer cells CCG-1423 metastasis |
| title | Enriching the Arsenal of Pharmacological Tools against MICAL2 |
| title_full | Enriching the Arsenal of Pharmacological Tools against MICAL2 |
| title_fullStr | Enriching the Arsenal of Pharmacological Tools against MICAL2 |
| title_full_unstemmed | Enriching the Arsenal of Pharmacological Tools against MICAL2 |
| title_short | Enriching the Arsenal of Pharmacological Tools against MICAL2 |
| title_sort | enriching the arsenal of pharmacological tools against mical2 |
| topic | MICAL2 wound healing assay HMEC-1 endothelial cells 786-O kidney cancer cells CCG-1423 metastasis |
| url | https://www.mdpi.com/1420-3049/26/24/7519 |
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