Design, Synthesis and Evaluation of Antioxidant and NSAID Derivatives with Antioxidant, Anti-Inflammatory and Plasma Lipid Lowering Effects
Amides containing methyl esters of γ-aminobutyric acid (GABA), L-proline and L-tyrosine, and esters containing 3-(pyridin-3-yl)propan-1-ol were synthesized by conjugation with 3,5-di-<i>tert</i>-butyl-4-hydroxybenzoic, an NSAID (tolfenamic acid), or 3-phenylacrylic (cinnamic, (<i>E...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-02-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/29/5/1016 |
| _version_ | 1797264178167152640 |
|---|---|
| author | Panagiotis Theodosis-Nobelos Gabriel Marc Eleni A. Rekka |
| author_facet | Panagiotis Theodosis-Nobelos Gabriel Marc Eleni A. Rekka |
| author_sort | Panagiotis Theodosis-Nobelos |
| collection | DOAJ |
| description | Amides containing methyl esters of γ-aminobutyric acid (GABA), L-proline and L-tyrosine, and esters containing 3-(pyridin-3-yl)propan-1-ol were synthesized by conjugation with 3,5-di-<i>tert</i>-butyl-4-hydroxybenzoic, an NSAID (tolfenamic acid), or 3-phenylacrylic (cinnamic, (<i>E</i>)-3-(3,4-dimethoxyphenyl)acrylic and caffeic) acids. The rationale for the conjugation of such moieties was based on the design of structures with two or more molecular characteristics. The novel compounds were tested for their antioxidant, anti-inflammatory and hypolipidemic properties. Several compounds were potent antioxidants, comparable to the well-known antioxidant, Trolox. In addition, the radical scavenging activity of compound <b>6</b> reached levels that were slightly better than that of Trolox. All the tested compounds demonstrated remarkable activity in the reduction in carrageenan-induced rat paw edema, up to 59% (compound <b>2</b>, a dual antioxidant and anti-inflammatory molecule, with almost 2.5-times higher activity in this experiment than the parent NSAID). Additionally, the compounds caused a significant decrease in the plasma lipidemic indices in Triton-induced hyperlipidemic rats. Compound <b>2</b> decreased total cholesterol by 75.1% and compound <b>3</b> decreased triglycerides by 79.3% at 150 μmol/kg (i.p.). The hypocholesterolemic effect of the compounds was comparable to that of simvastatin, a well-known hypocholesterolemic drug. Additionally, all compounds lowered blood triglycerides. The synthesized compounds with multiple activities, as designed, may be useful as potential candidates for conditions involving inflammation, lipidemic deregulation and oxygen toxicity. |
| first_indexed | 2024-04-25T00:24:46Z |
| format | Article |
| id | doaj.art-b91f5d5c3e0b43bb8192bd9c5a0a9da8 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-25T00:24:46Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b91f5d5c3e0b43bb8192bd9c5a0a9da82024-03-12T16:50:46ZengMDPI AGMolecules1420-30492024-02-01295101610.3390/molecules29051016Design, Synthesis and Evaluation of Antioxidant and NSAID Derivatives with Antioxidant, Anti-Inflammatory and Plasma Lipid Lowering EffectsPanagiotis Theodosis-Nobelos0Gabriel Marc1Eleni A. Rekka2Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia 1036, CyprusDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, RO-400010 Cluj-Napoca, RomaniaDepartment of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, 54124 Thessaloniki, GreeceAmides containing methyl esters of γ-aminobutyric acid (GABA), L-proline and L-tyrosine, and esters containing 3-(pyridin-3-yl)propan-1-ol were synthesized by conjugation with 3,5-di-<i>tert</i>-butyl-4-hydroxybenzoic, an NSAID (tolfenamic acid), or 3-phenylacrylic (cinnamic, (<i>E</i>)-3-(3,4-dimethoxyphenyl)acrylic and caffeic) acids. The rationale for the conjugation of such moieties was based on the design of structures with two or more molecular characteristics. The novel compounds were tested for their antioxidant, anti-inflammatory and hypolipidemic properties. Several compounds were potent antioxidants, comparable to the well-known antioxidant, Trolox. In addition, the radical scavenging activity of compound <b>6</b> reached levels that were slightly better than that of Trolox. All the tested compounds demonstrated remarkable activity in the reduction in carrageenan-induced rat paw edema, up to 59% (compound <b>2</b>, a dual antioxidant and anti-inflammatory molecule, with almost 2.5-times higher activity in this experiment than the parent NSAID). Additionally, the compounds caused a significant decrease in the plasma lipidemic indices in Triton-induced hyperlipidemic rats. Compound <b>2</b> decreased total cholesterol by 75.1% and compound <b>3</b> decreased triglycerides by 79.3% at 150 μmol/kg (i.p.). The hypocholesterolemic effect of the compounds was comparable to that of simvastatin, a well-known hypocholesterolemic drug. Additionally, all compounds lowered blood triglycerides. The synthesized compounds with multiple activities, as designed, may be useful as potential candidates for conditions involving inflammation, lipidemic deregulation and oxygen toxicity.https://www.mdpi.com/1420-3049/29/5/1016antioxidantsNSAIDanti-inflammatorydyslipidemiaantioxidant activitypluripotent derivatives |
| spellingShingle | Panagiotis Theodosis-Nobelos Gabriel Marc Eleni A. Rekka Design, Synthesis and Evaluation of Antioxidant and NSAID Derivatives with Antioxidant, Anti-Inflammatory and Plasma Lipid Lowering Effects Molecules antioxidants NSAID anti-inflammatory dyslipidemia antioxidant activity pluripotent derivatives |
| title | Design, Synthesis and Evaluation of Antioxidant and NSAID Derivatives with Antioxidant, Anti-Inflammatory and Plasma Lipid Lowering Effects |
| title_full | Design, Synthesis and Evaluation of Antioxidant and NSAID Derivatives with Antioxidant, Anti-Inflammatory and Plasma Lipid Lowering Effects |
| title_fullStr | Design, Synthesis and Evaluation of Antioxidant and NSAID Derivatives with Antioxidant, Anti-Inflammatory and Plasma Lipid Lowering Effects |
| title_full_unstemmed | Design, Synthesis and Evaluation of Antioxidant and NSAID Derivatives with Antioxidant, Anti-Inflammatory and Plasma Lipid Lowering Effects |
| title_short | Design, Synthesis and Evaluation of Antioxidant and NSAID Derivatives with Antioxidant, Anti-Inflammatory and Plasma Lipid Lowering Effects |
| title_sort | design synthesis and evaluation of antioxidant and nsaid derivatives with antioxidant anti inflammatory and plasma lipid lowering effects |
| topic | antioxidants NSAID anti-inflammatory dyslipidemia antioxidant activity pluripotent derivatives |
| url | https://www.mdpi.com/1420-3049/29/5/1016 |
| work_keys_str_mv | AT panagiotistheodosisnobelos designsynthesisandevaluationofantioxidantandnsaidderivativeswithantioxidantantiinflammatoryandplasmalipidloweringeffects AT gabrielmarc designsynthesisandevaluationofantioxidantandnsaidderivativeswithantioxidantantiinflammatoryandplasmalipidloweringeffects AT eleniarekka designsynthesisandevaluationofantioxidantandnsaidderivativeswithantioxidantantiinflammatoryandplasmalipidloweringeffects |