Antioxidant Serine-(NSAID) Hybrids with Anti-Inflammatory and Hypolipidemic Potency
A series of L-serine amides of antioxidant acids, such as Trolox, (<i>E</i>)-3-(3,5-di-<i>tert</i>-butyl-4-hydroxyphenyl)acrylic acid (phenolic derivative of cinnamic acid) and 3,5-di-<i>tert</i>-butyl-4-hydroxybenzoic acid (structurally similar to butylated hydro...
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MDPI AG
2021-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/13/4060 |
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| author | Panagiotis Theodosis-Nobelos Georgios Papagiouvannis Paraskevi Tziona Panos N. Kourounakis Eleni A. Rekka |
| author_facet | Panagiotis Theodosis-Nobelos Georgios Papagiouvannis Paraskevi Tziona Panos N. Kourounakis Eleni A. Rekka |
| author_sort | Panagiotis Theodosis-Nobelos |
| collection | DOAJ |
| description | A series of L-serine amides of antioxidant acids, such as Trolox, (<i>E</i>)-3-(3,5-di-<i>tert</i>-butyl-4-hydroxyphenyl)acrylic acid (phenolic derivative of cinnamic acid) and 3,5-di-<i>tert</i>-butyl-4-hydroxybenzoic acid (structurally similar to butylated hydroxytoluene), was synthesized. The hydroxy group of serine was esterified with two classical NSAIDs, ibuprofen and ketoprofen. The Trolox derivatives with ibuprofen (7) and ketoprofen (10) were the most potent inhibitors of lipid peroxidation (IC<sub>50</sub> 3.4 μΜ and 2.8 μΜ), several times more potent than the reference Trolox (IC<sub>50</sub> 25 μΜ). Most of the compounds decreased carrageenan-induced rat paw edema (37–67% at 150 μmol/kg). They were moderate inhibitors of soybean lipoxygenase, with the exception of ibuprofen derivative 8 (IC<sub>50</sub> 13 μΜ). The most active anti-inflammatory compounds exhibited a significant decrease in lipidemic indices in the plasma of Triton-induced hyperlipidemic rats, e.g., the most active compound 9 decreased triglycerides, total cholesterol and low-density lipoprotein cholesterol by 52%, 61% and 70%, respectively, at 150 μmol/kg (i.p.), similar to that of simvastatin, a well-known hypocholesterolemic drug. Since the designed compounds seem to exhibit multiple pharmacological actions, they may be of use for the development of agents against inflammatory and degenerative conditions. |
| first_indexed | 2024-03-10T09:50:46Z |
| format | Article |
| id | doaj.art-65e2bdcb4adf430d90e113bb890447e9 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T09:50:46Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-65e2bdcb4adf430d90e113bb890447e92023-11-22T02:47:26ZengMDPI AGMolecules1420-30492021-07-012613406010.3390/molecules26134060Antioxidant Serine-(NSAID) Hybrids with Anti-Inflammatory and Hypolipidemic PotencyPanagiotis Theodosis-Nobelos0Georgios Papagiouvannis1Paraskevi Tziona2Panos N. Kourounakis3Eleni A. Rekka4Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia 1036, CyprusDepartment of Pharmacy, School of Health Sciences, Frederick University, Nicosia 1036, CyprusDepartment of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Pharmacy, School of Health Sciences, Frederick University, Nicosia 1036, CyprusDepartment of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, 54124 Thessaloniki, GreeceA series of L-serine amides of antioxidant acids, such as Trolox, (<i>E</i>)-3-(3,5-di-<i>tert</i>-butyl-4-hydroxyphenyl)acrylic acid (phenolic derivative of cinnamic acid) and 3,5-di-<i>tert</i>-butyl-4-hydroxybenzoic acid (structurally similar to butylated hydroxytoluene), was synthesized. The hydroxy group of serine was esterified with two classical NSAIDs, ibuprofen and ketoprofen. The Trolox derivatives with ibuprofen (7) and ketoprofen (10) were the most potent inhibitors of lipid peroxidation (IC<sub>50</sub> 3.4 μΜ and 2.8 μΜ), several times more potent than the reference Trolox (IC<sub>50</sub> 25 μΜ). Most of the compounds decreased carrageenan-induced rat paw edema (37–67% at 150 μmol/kg). They were moderate inhibitors of soybean lipoxygenase, with the exception of ibuprofen derivative 8 (IC<sub>50</sub> 13 μΜ). The most active anti-inflammatory compounds exhibited a significant decrease in lipidemic indices in the plasma of Triton-induced hyperlipidemic rats, e.g., the most active compound 9 decreased triglycerides, total cholesterol and low-density lipoprotein cholesterol by 52%, 61% and 70%, respectively, at 150 μmol/kg (i.p.), similar to that of simvastatin, a well-known hypocholesterolemic drug. Since the designed compounds seem to exhibit multiple pharmacological actions, they may be of use for the development of agents against inflammatory and degenerative conditions.https://www.mdpi.com/1420-3049/26/13/4060antioxidant serine conjugatesinflammationlipoxygenase inhibitiondyslipidemiaantioxidant activityanti-inflammatory agents |
| spellingShingle | Panagiotis Theodosis-Nobelos Georgios Papagiouvannis Paraskevi Tziona Panos N. Kourounakis Eleni A. Rekka Antioxidant Serine-(NSAID) Hybrids with Anti-Inflammatory and Hypolipidemic Potency Molecules antioxidant serine conjugates inflammation lipoxygenase inhibition dyslipidemia antioxidant activity anti-inflammatory agents |
| title | Antioxidant Serine-(NSAID) Hybrids with Anti-Inflammatory and Hypolipidemic Potency |
| title_full | Antioxidant Serine-(NSAID) Hybrids with Anti-Inflammatory and Hypolipidemic Potency |
| title_fullStr | Antioxidant Serine-(NSAID) Hybrids with Anti-Inflammatory and Hypolipidemic Potency |
| title_full_unstemmed | Antioxidant Serine-(NSAID) Hybrids with Anti-Inflammatory and Hypolipidemic Potency |
| title_short | Antioxidant Serine-(NSAID) Hybrids with Anti-Inflammatory and Hypolipidemic Potency |
| title_sort | antioxidant serine nsaid hybrids with anti inflammatory and hypolipidemic potency |
| topic | antioxidant serine conjugates inflammation lipoxygenase inhibition dyslipidemia antioxidant activity anti-inflammatory agents |
| url | https://www.mdpi.com/1420-3049/26/13/4060 |
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