Chimeric Small Molecules for Detouring Drugs into Mitochondria to Engender Apoptosis in Cancer Cells.
Chembiochem
; 25(2): e202300603, 2024 01 15.
Article
em En
| MEDLINE
| ID: mdl-37934785
Mitochondrion has appeared as one of the important targets for anti-cancer therapy. Subsequently, small molecule anti-cancer drugs are directed to the mitochondria for improved therapeutic efficacy. However, simultaneous imaging and impairing mitochondria by a single probe remained a major challenge. To address this, herein Chimeric Small Molecules (CSMs) encompassing drugs, fluorophore and mitochondria homing moiety were designed and synthesized through a concise strategy. Screening of the CSMs in a panel of cancer cell lines (HeLa, MCF7, A549, and HCT-116) revealed that one of the CSMs comprising Indomethacin V exhibited remarkable cervical cancer cell (HeLa) killing (IC50 =0.97â
µM). This lead CSM homed into the mitochondria of HeLa cells within 1â
h followed by mitochondrial damage and reactive oxygen species (ROS) generation. This novel Indomethacin V-based CSM-mediated mitochondrial damage induced programmed cell death (apoptosis). We anticipate these CSMs can be used as tools to understand the drug effects in organelle chemical biology in diseased states.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Chembiochem
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Índia