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

Grande, Fedora; Giordano, Francesca; Occhiuzzi, Maria Antonietta; Rocca, Carmine; Ioele, Giuseppina; Luca, Michele De; Ragno, Gaetano; Panno, Maria Luisa; Rizzuti, Bruno; Garofalo, Antonio

doi:10.3390/molecules26133940

Cited by 7 publications

(4 citation statements)

References 55 publications

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“…This analysis is based on the production of Prostaglandin F2α by SnCl 2 (Tin II chloride) reduction of COX-derived Prostaglandin H2 in the COX reaction. Both ovine COX-1 and human recombinant COX-2 enzymes were tested separately in this assay [ 91 ]. The results were expressed in the percentage of inhibition of COX-1 and -2, and IC 50 was calculated (mg C3GE/L).…”

Section: Methodsmentioning

confidence: 99%

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Mexican Native Black Bean Anthocyanin-Rich Extracts Modulate Biological Markers Associated with Inflammation

et al. 2023

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This work aimed to obtain and characterize anthocyanin-rich extracts (ARE) from native black beans and evaluate their antioxidant and anti-inflammatory potential. The initial extract was obtained by supercritical fluids (RE) and purified using Amberlite® XAD-7 resin (PE). RE and PE were fractionated using countercurrent chromatography, and four fractions were obtained (REF1 and REF2 from RE, PEF1, and PEF2 from PE). ARE and fractions were characterized, and the biological potential was evaluated. ABTS IC50 values ranged from 7.9 to 139.2 (mg C3GE/L), DPPH IC50 ranged from 9.2 to 117.2 (mg C3GE/L), and NO IC50 ranged from 0.6 to143.8 (mg C3GE/L) (p < 0.05). COX-1 IC50 ranged from 0.1 to 0.9 (mg C3GE/L), COX-2 IC50 ranged from 0.01 to 0.7 (mg C3GE/L), and iNOS IC50 ranged from 0.9 to 5.6 (mg C3GE/L) (p < 0.05). The theoretical binding energy for phenolic compounds ranged from −8.45 to −1.4 kcal/mol for COX-1, from −8.5 to −1.8 kcal/mol for COX-2, and from −7.2 to −1.6 kcal/mol for iNOS. RE and REF2 presented the highest antioxidant and anti-inflammatory potential. Countercurrent chromatography effectively isolates and purifies bioactive compounds while maintaining their biological potential. Native black beans present an attractive phytochemical profile and could be used as ingredients in nutraceuticals and functional foods.

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Section: Methodsmentioning

confidence: 99%

“…Flexible torsions, charges, and grid size were assigned using Autodock Tools. Docking calculations were performed using Autodock Vina, and the binding pose with the lowest binding energy was selected to be visualized using Discovery Studio visualizer software 4.0 (Accelrys Inc., CA, USA) [ 91 , 92 ].…”

Section: Methodsmentioning

confidence: 99%

Mexican Native Black Bean Anthocyanin-Rich Extracts Modulate Biological Markers Associated with Inflammation

et al. 2023

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“…Although the formation of the active metabolite 4 has been conclusively ascertained, the overall pathway through which this occurs has long remained unclear. The active metabolite 4 was found to be active on both COX isoforms (COX-1 and COX-2), with a marked preference for COX-2 [ 20 ]. Indeed, the conversion must necessarily take place through a carbon–carbon bond cleavage, which is known to be a rather rare reaction occurring during mammalian metabolism.…”

Section: Resultsmentioning

confidence: 99%

Dissecting CYP1A2 Activation by Arylalkanoic Acid Prodrugs toward the Development of Anti-Inflammatory Agents

Occhiuzzi,

Ioele,

De Luca

et al. 2023

IJMS

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Arylalkane-derived prodrugs of arylacetic acids are a small group of substances that have long been known for their anti-inflammatory action. Despite their ease of synthesis and good potential for the development of new potent and safe anti-inflammatory agents, this group of substances has not received much attention from researchers so far. Therefore, representative arylalkane derivatives were investigated through molecular docking techniques to verify the possible hepatic activation mode toward active metabolites by CYP1A2. In this regard, arylalkanoic acid prodrugs were docked with a crystallographic structure of human CYP1A2, in which the enzyme is co-crystallized with the selective competitive inhibitor α-naphthoflavone BHF. Of note, all the examined compounds proved capable of interacting with the enzyme active site in a manner similar to Nabumetone, thus confirming that a productive metabolic transformation is feasible. On the basis of these findings, it is possible to argue that subtle differences in the way CYP1A2 accommodates the ligands depend on the fine details of their molecular structures. Overall, these data suggest that compounds simply formed by an aromatic moiety bearing an appropriate alkane-derived chain could lead to innovative anti-inflammatory agents.

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“…Recently, the use of NSAIDs has been safely used to relieve symptoms in patients with suspicion of Covid-19, and has not been associated with mortality or ventilator care in these patients [ 4 ]. Other pharmacological activities of NSAIDs are well recognized, such as the inhibitory effect on carcinogenesis and cancer spreading due to different mechanisms, including the induction of cell proliferation, apoptosis inhibition, and host’s immune response suppression [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Photodegradation of Anti-Inflammatory Drugs: Stability Tests and Lipid Nanocarriers for Their Photoprotection

et al. 2021

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The present paper provides an updated overview of the methodologies applied in photodegradation studies of non-steroidal anti-inflammatory drugs. Photostability tests, performed according to international standards, have clearly demonstrated the photolability of many drugs belonging to this class, observed during the preparation of commercial forms, administration or when dispersed in the environment. The photodegradation profile of these drugs is usually monitored by spectrophotometric or chromatographic techniques and in many studies the analytical data are processed by chemometric procedures. The application of multivariate analysis in the resolution of often-complex data sets makes it possible to estimate the pure spectra of the species involved in the degradation process and their concentration profiles. Given the wide use of these drugs, several pharmaceutical formulations have been investigated to improve their photostability in solution or gel, as well as the pharmacokinetic profile. The use of lipid nanocarriers as liposomes, niosomes or solid lipid nanoparticles has demonstrated to both minimize photodegradation and improve the controlled release of the entrapped drugs.

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

Cited by 7 publications

References 55 publications

Mexican Native Black Bean Anthocyanin-Rich Extracts Modulate Biological Markers Associated with Inflammation

Mexican Native Black Bean Anthocyanin-Rich Extracts Modulate Biological Markers Associated with Inflammation

Dissecting CYP1A2 Activation by Arylalkanoic Acid Prodrugs toward the Development of Anti-Inflammatory Agents

Photodegradation of Anti-Inflammatory Drugs: Stability Tests and Lipid Nanocarriers for Their Photoprotection

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