Toward Multitasking Pharmacological COX-Targeting Agents: Non-Steroidal Anti-Inflammatory Prodrugs with Antiproliferative Effects

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 thro...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2021-06, Vol.26 (13), p.3940
Main Authors: Grande, Fedora, Giordano, Francesca, Occhiuzzi, Maria Antonietta, Rocca, Carmine, Ioele, Giuseppina, De Luca, Michele, Ragno, Gaetano, Panno, Maria Luisa, Rizzuti, Bruno, Garofalo, Antonio
Format: Article
Language:English
Subjects:
anti-enzymatic assays
Anti-inflammatory agents
Antiproliferatives
Antitumor activity
Apoptosis
Cancer
Cell growth
cell toxicity
COX-1
COX-2
Cytotoxicity
Drugs
Enzymes
Formulations
Growth factors
Inflammation
Metabolism
Metabolites
Metastasis
molecular docking
Multitasking
nabumetone
Physiology
Prodrugs
Toxicity
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Summary: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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules26133940