Toward Multitasking Pharmacological COX-Targeting Agents: Non-Steroidal Anti-Inflammatory Prodrugs with Antiproliferative Effects.
Molecules
; 26(13)2021 Jun 28.
Article
em En
| MEDLINE
| ID: mdl-34203324
ABSTRACT
The antitumor activity of certain anti-inflammatory drugs is often attributed to an indirect effect based on the inhibition of COX enzymes. In the case of anti-inflammatory prodrugs, this property could be attributed to the parent molecules with mechanism other than COX inhibition, particularly through formulations capable of slowing down their metabolic conversion. In this work, a pilot docking study aimed at comparing the interaction of two prodrugs, nabumetone (NB) and its tricyclic analog 7-methoxy-2,3-dihydro-1H-cyclopenta[b]naphthalen-1-one (MC), and their common active metabolite 6-methoxy-2-naphthylacetic acid (MNA) with the COX binding site, was carried out. Cytotoxicity, cytofluorimetry, and protein expression assays on prodrugs were also performed to assess their potential as antiproliferative agents that could help hypothesize an effective use as anticancer therapeutics. Encouraging results suggest that the studied compounds could act not only as precursors of the anti-inflammatory metabolite, but also as direct antiproliferative agents.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anti-Inflamatórios não Esteroides
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Inibidores de Ciclo-Oxigenase
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Proliferação de Células
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Nabumetona
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article