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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412087/ https://www.ncbi.nlm.nih.gov/pubmed/32635622 http://dx.doi.org/10.3390/molecules25133066 |
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author | Seghetti, Francesca Di Martino, Rita Maria Concetta Catanzaro, Elena Bisi, Alessandra Gobbi, Silvia Rampa, Angela Canonico, Barbara Montanari, Mariele Krysko, Dmitri V. Papa, Stefano Fimognari, Carmela Belluti, Federica |
author_facet | Seghetti, Francesca Di Martino, Rita Maria Concetta Catanzaro, Elena Bisi, Alessandra Gobbi, Silvia Rampa, Angela Canonico, Barbara Montanari, Mariele Krysko, Dmitri V. Papa, Stefano Fimognari, Carmela Belluti, Federica |
author_sort | Seghetti, Francesca |
collection | PubMed |
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 1, bearing a para-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 1 as a lead compound worth to be progressed as an anticancer drug candidate. |
format | Online Article Text |
id | pubmed-7412087 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74120872020-08-25 Curcumin-1,2,3-Triazole Conjugation for Targeting the Cancer Apoptosis Machinery Seghetti, Francesca Di Martino, Rita Maria Concetta Catanzaro, Elena Bisi, Alessandra Gobbi, Silvia Rampa, Angela Canonico, Barbara Montanari, Mariele Krysko, Dmitri V. Papa, Stefano Fimognari, Carmela Belluti, Federica Molecules Article 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 1, bearing a para-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 1 as a lead compound worth to be progressed as an anticancer drug candidate. MDPI 2020-07-05 /pmc/articles/PMC7412087/ /pubmed/32635622 http://dx.doi.org/10.3390/molecules25133066 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Seghetti, Francesca Di Martino, Rita Maria Concetta Catanzaro, Elena Bisi, Alessandra Gobbi, Silvia Rampa, Angela Canonico, Barbara Montanari, Mariele Krysko, Dmitri V. Papa, Stefano Fimognari, Carmela Belluti, Federica Curcumin-1,2,3-Triazole Conjugation for Targeting the Cancer Apoptosis Machinery |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412087/ https://www.ncbi.nlm.nih.gov/pubmed/32635622 http://dx.doi.org/10.3390/molecules25133066 |
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