Breast cancer is the most diagnosed type of cancer among women for which an exhaustive cure has not been discovered yet. Nowadays, tamoxifen still represents the gold standard for breast cancer therapy; it acts on both estrogen receptor-positive and estrogen receptor-negative breast cancers. Unfortunately, its toxicity and the related chemoresistance undermine its antitumor potential. In this paper, new tamoxifen-based derivatives with a rigid structural motif in their structure were designed, synthesized, and evaluated to assess their antitumor behavior. All the tested compounds affected estrogen receptor-positive tumor (MCF-7) cell growth, even with different extents, among which, the most active ones proved also to induce mitochondria-mediated apoptosis through activation of PARP cleavage, decrease in Bax/Bcl-2 ratio and increase in Bim gene expression levels. Here we found that the compound 1, carrying a rigid xanthene core, turned out to be the most promising of the set showing an activity profile comparable to that of tamoxifen. Furthermore, a more favorable genotoxic profile than tamoxifen made compound 1 a promising candidate for further studies.

Identification of a new tamoxifen-xanthene hybrid as pro-apoptotic anticancer agent / Catanzaro E.; Seghetti F.; Calcabrini C.; Rampa A.; Gobbi S.; Sestili P.; Turrini E.; Maffei F.; Hrelia P.; Bisi A.; Belluti F.; Fimognari C.. - In: BIOORGANIC CHEMISTRY. - ISSN 0045-2068. - STAMPA. - 86:(2019), pp. 538-549. [10.1016/j.bioorg.2019.02.017]

Identification of a new tamoxifen-xanthene hybrid as pro-apoptotic anticancer agent

Catanzaro E.;Seghetti F.;Calcabrini C.;Rampa A.;Gobbi S.;Turrini E.;Maffei F.;Hrelia P.;Bisi A.;Belluti F.
;
Fimognari C.
2019

Abstract

Breast cancer is the most diagnosed type of cancer among women for which an exhaustive cure has not been discovered yet. Nowadays, tamoxifen still represents the gold standard for breast cancer therapy; it acts on both estrogen receptor-positive and estrogen receptor-negative breast cancers. Unfortunately, its toxicity and the related chemoresistance undermine its antitumor potential. In this paper, new tamoxifen-based derivatives with a rigid structural motif in their structure were designed, synthesized, and evaluated to assess their antitumor behavior. All the tested compounds affected estrogen receptor-positive tumor (MCF-7) cell growth, even with different extents, among which, the most active ones proved also to induce mitochondria-mediated apoptosis through activation of PARP cleavage, decrease in Bax/Bcl-2 ratio and increase in Bim gene expression levels. Here we found that the compound 1, carrying a rigid xanthene core, turned out to be the most promising of the set showing an activity profile comparable to that of tamoxifen. Furthermore, a more favorable genotoxic profile than tamoxifen made compound 1 a promising candidate for further studies.
2019
Identification of a new tamoxifen-xanthene hybrid as pro-apoptotic anticancer agent / Catanzaro E.; Seghetti F.; Calcabrini C.; Rampa A.; Gobbi S.; Sestili P.; Turrini E.; Maffei F.; Hrelia P.; Bisi A.; Belluti F.; Fimognari C.. - In: BIOORGANIC CHEMISTRY. - ISSN 0045-2068. - STAMPA. - 86:(2019), pp. 538-549. [10.1016/j.bioorg.2019.02.017]
Catanzaro E.; Seghetti F.; Calcabrini C.; Rampa A.; Gobbi S.; Sestili P.; Turrini E.; Maffei F.; Hrelia P.; Bisi A.; Belluti F.; Fimognari C.
File in questo prodotto:
Eventuali allegati, non sono esposti

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/700802
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 18
social impact