Curcumin-1,2,3-Triazole Conjugation for Targeting the Cancer Apoptosis Machinery
The burden of neoplastic diseases is widely recognized as a severe cause of mortality. The clinical inadequacy of most anticancer therapeutics urgently prompted intense drug discovery efforts toward the identification of new chemical entities endowed with a potent and safe antitumor profile. In this...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/13/3066 |
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| author | Francesca Seghetti Rita Maria Concetta Di Martino Elena Catanzaro Alessandra Bisi Silvia Gobbi Angela Rampa Barbara Canonico Mariele Montanari Dmitri V. Krysko Stefano Papa Carmela Fimognari Federica Belluti |
| author_facet | Francesca Seghetti Rita Maria Concetta Di Martino Elena Catanzaro Alessandra Bisi Silvia Gobbi Angela Rampa Barbara Canonico Mariele Montanari Dmitri V. Krysko Stefano Papa Carmela Fimognari Federica Belluti |
| author_sort | Francesca Seghetti |
| collection | DOAJ |
| description | The burden of neoplastic diseases is widely recognized as a severe cause of mortality. The clinical inadequacy of most anticancer therapeutics urgently prompted intense drug discovery efforts toward the identification of new chemical entities endowed with a potent and safe antitumor profile. In this scenario, targeting cancer cells apoptosis machinery has emerged as a relevant strategy, useful for tackling the emergence of drug resistance. On this basis, a small library of naturally inspired hybrid molecules was obtained by combining, through a click chemistry approach, “privileged” synthons such as curcumin scaffold and 1,2,3-triazole building block. Compound <b>1</b>, bearing a <i>para</i>-fluoro phenyl moiety, showed low-micromolar potency against T acute lymphoblastic leukemia cell growth. More in-depth biologic studies demonstrated, for this analog, cell death-inducing properties associated with its capability to simultaneously activate both the receptor and the mitochondrial apoptosis cascades. This peculiar behavior offers promises for achieving an expanded anticancer effect, namely intense cytotoxic response coupled with reduced predisposition of chemoresistance insurgence. Altogether, this study allowed the identification of compound <b>1</b> as a lead compound worth to be progressed as an anticancer drug candidate. |
| first_indexed | 2024-03-10T18:40:46Z |
| format | Article |
| id | doaj.art-9a79b61846734e9dbe01cea2a04d770b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T18:40:46Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9a79b61846734e9dbe01cea2a04d770b2023-11-20T05:53:53ZengMDPI AGMolecules1420-30492020-07-012513306610.3390/molecules25133066Curcumin-1,2,3-Triazole Conjugation for Targeting the Cancer Apoptosis MachineryFrancesca Seghetti0Rita Maria Concetta Di Martino1Elena Catanzaro2Alessandra Bisi3Silvia Gobbi4Angela Rampa5Barbara Canonico6Mariele Montanari7Dmitri V. Krysko8Stefano Papa9Carmela Fimognari10Federica Belluti11Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126 Bologna, ItalyDepartment for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d’Augusto 237, 47921 Rimini, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126 Bologna, ItalyDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Via Ca’ Le Suore, 2, 61029 Urbino, ItalyDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Via Ca’ Le Suore, 2, 61029 Urbino, ItalyCell Death Investigation and Therapy Laboratory, Department of Human Structure and Repair, Ghent University, 9000 Ghent, BelgiumDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Via Ca’ Le Suore, 2, 61029 Urbino, ItalyDepartment for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d’Augusto 237, 47921 Rimini, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126 Bologna, ItalyThe burden of neoplastic diseases is widely recognized as a severe cause of mortality. The clinical inadequacy of most anticancer therapeutics urgently prompted intense drug discovery efforts toward the identification of new chemical entities endowed with a potent and safe antitumor profile. In this scenario, targeting cancer cells apoptosis machinery has emerged as a relevant strategy, useful for tackling the emergence of drug resistance. On this basis, a small library of naturally inspired hybrid molecules was obtained by combining, through a click chemistry approach, “privileged” synthons such as curcumin scaffold and 1,2,3-triazole building block. Compound <b>1</b>, bearing a <i>para</i>-fluoro phenyl moiety, showed low-micromolar potency against T acute lymphoblastic leukemia cell growth. More in-depth biologic studies demonstrated, for this analog, cell death-inducing properties associated with its capability to simultaneously activate both the receptor and the mitochondrial apoptosis cascades. This peculiar behavior offers promises for achieving an expanded anticancer effect, namely intense cytotoxic response coupled with reduced predisposition of chemoresistance insurgence. Altogether, this study allowed the identification of compound <b>1</b> as a lead compound worth to be progressed as an anticancer drug candidate.https://www.mdpi.com/1420-3049/25/13/3066apoptosiscell cyclecell deathclick chemistrycurcuminflow cytometry |
| spellingShingle | Francesca Seghetti Rita Maria Concetta Di Martino Elena Catanzaro Alessandra Bisi Silvia Gobbi Angela Rampa Barbara Canonico Mariele Montanari Dmitri V. Krysko Stefano Papa Carmela Fimognari Federica Belluti Curcumin-1,2,3-Triazole Conjugation for Targeting the Cancer Apoptosis Machinery Molecules apoptosis cell cycle cell death click chemistry curcumin flow cytometry |
| title | Curcumin-1,2,3-Triazole Conjugation for Targeting the Cancer Apoptosis Machinery |
| title_full | Curcumin-1,2,3-Triazole Conjugation for Targeting the Cancer Apoptosis Machinery |
| title_fullStr | Curcumin-1,2,3-Triazole Conjugation for Targeting the Cancer Apoptosis Machinery |
| title_full_unstemmed | Curcumin-1,2,3-Triazole Conjugation for Targeting the Cancer Apoptosis Machinery |
| title_short | Curcumin-1,2,3-Triazole Conjugation for Targeting the Cancer Apoptosis Machinery |
| title_sort | curcumin 1 2 3 triazole conjugation for targeting the cancer apoptosis machinery |
| topic | apoptosis cell cycle cell death click chemistry curcumin flow cytometry |
| url | https://www.mdpi.com/1420-3049/25/13/3066 |
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