Identification of two novel thiophene analogues as inducers of autophagy mediated cell death in breast cancer cells.
Bioorg Med Chem
; 37: 116112, 2021 05 01.
Article
em En
| MEDLINE
| ID: mdl-33751939
ABSTRACT
Natural compounds isolated from different medicinal plants remain one of the major resources of anticancer drugs due to their enormous chemical diversity. Studies suggested therapeutic potential for various tanshinones, key bioactive lipophilic compounds from the root extracts of Salvia miltiorrhiza Bunge, against multiple cancers including breast carcinoma. We designed, synthesized and evaluated anti-cancer properties of a series of condensed and doubly condensed furophenanthraquinones of tanshinone derivatives on two breast cancer lines - MCF7 and MDA-MB-231. We identified two thiophene analogues - compounds 48 and 52 with greater anti-proliferative efficiency (~4 fold) as compared to the natural tanshinones. Mechanistically, we showed that both compounds induced autophagy mediated cell death and partial but significant restoration of cell death in the presence of autophagy inhibitor further supported this notion. Both compounds transcriptionally activated several autophagy genes responsible for autophagosome formation along with two death regulators - GADD34 and CHOP for inducing cell death. Altogether, our studies provide strong evidence to support compounds 48 and 52 as promising leads for further development as anticancer agents through modulating autophagy mechanism.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Tiofenos
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Neoplasias da Mama
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Antineoplásicos
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article