Multifaceted activity of polyciclic MDR revertant agents in drug-resistant leukemic cells: Role of the spacer.
Bioorg Chem
; 106: 104460, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-33229118
ABSTRACT
A small library of derivatives carrying a polycyclic scaffold recently identified by us as a new privileged structure in medicinal chemistry was designed and synthesized, aiming at obtaining potent MDR reverting agents also endowed with antitumor properties. In particular, as a follow-up of our previous studies, attention was focused on the role of the spacer connecting the polycyclic core with a properly selected nitrogen-containing group. A relevant increase in reverting potency was observed, going from the previously employed but-2-ynyl- to a pent-3-ynylamino moiety, as in compounds 3d and 3e, while the introduction of a triazole ring proved to differently impact on the activity of the compounds. The docking results supported the data obtained by biological tests, showing, for the most active compounds, the ability to establish specific bonds with P-glycoprotein. Moreover, a multifaceted anticancer profile and dual in vitro activity was observed for all compounds, showing both revertant and antitumor effects on leukemic cells. In this respect, 3c emerged as a "triple-target" agent, endowed with a relevant reverting potency, a considerable antiproliferative activity and a collateral sensitivity profile.
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Base de dados:
MEDLINE
Assunto principal:
Succinimidas
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Hidrocarbonetos Aromáticos com Pontes
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Resistência a Múltiplos Medicamentos
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Resistencia a Medicamentos Antineoplásicos
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Antracenos
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Antineoplásicos
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article