Design, Synthesis, In Silico and In Vitro Studies for New Nitric Oxide-Releasing Indomethacin Derivatives with 1,3,4-Oxadiazole-2-thiol Scaffold
Starting from indomethacin (IND), one of the most prescribed non-steroidal anti-inflammatory drugs (NSAIDs), new nitric oxide-releasing indomethacin derivatives with 1,3,4-oxadiazole-2-thiol scaffold (NO-IND-OXDs, <b>8a–p</b>) have been developed as a safer and more efficient multitarget...
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/7079 |
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| author | Alexandru Sava Frederic Buron Sylvain Routier Alina Panainte Nela Bibire Sandra Mădălina Constantin Florentina Geanina Lupașcu Alin Viorel Focșa Lenuţa Profire |
| author_facet | Alexandru Sava Frederic Buron Sylvain Routier Alina Panainte Nela Bibire Sandra Mădălina Constantin Florentina Geanina Lupașcu Alin Viorel Focșa Lenuţa Profire |
| author_sort | Alexandru Sava |
| collection | DOAJ |
| description | Starting from indomethacin (IND), one of the most prescribed non-steroidal anti-inflammatory drugs (NSAIDs), new nitric oxide-releasing indomethacin derivatives with 1,3,4-oxadiazole-2-thiol scaffold (NO-IND-OXDs, <b>8a–p</b>) have been developed as a safer and more efficient multitarget therapeutic strategy. The successful synthesis of designed compounds (intermediaries and finals) was proved by complete spectroscopic analyses. In order to study the in silico interaction of NO-IND-OXDs with cyclooxygenase isoenzymes, a molecular docking study, using AutoDock 4.2.6 software, was performed. Moreover, their biological characterization, based on in vitro assays, in terms of thermal denaturation of serum proteins, antioxidant effects and the NO releasing capacity, was also performed. Based on docking results, <b>8k, 8l</b> and <b>8m</b> proved to be the best interaction for the COX-2 (cyclooxygense-2) target site, with an improved docking score compared with celecoxib. Referring to the thermal denaturation of serum proteins and antioxidant effects, all the tested compounds were more active than IND and aspirin, used as references. In addition, the compounds <b>8c</b>, <b>8h</b>, <b>8i</b>, <b>8m</b>, <b>8n</b> and <b>8o</b> showed increased capacity to release NO, which means they are safer in terms of gastrointestinal side effects. |
| first_indexed | 2024-03-10T09:55:05Z |
| format | Article |
| id | doaj.art-b5e62356e5ff4d23a24f8cdc49b850ec |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:55:05Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b5e62356e5ff4d23a24f8cdc49b850ec2023-11-22T02:28:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213707910.3390/ijms22137079Design, Synthesis, In Silico and In Vitro Studies for New Nitric Oxide-Releasing Indomethacin Derivatives with 1,3,4-Oxadiazole-2-thiol ScaffoldAlexandru Sava0Frederic Buron1Sylvain Routier2Alina Panainte3Nela Bibire4Sandra Mădălina Constantin5Florentina Geanina Lupașcu6Alin Viorel Focșa7Lenuţa Profire8Department of Analytical Chemistry, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 16 University Street, 700115 Iasi, RomaniaInstitut de Chimie Organique et Analytique ICOA, CNRS UMR 7311, Université d’Orléans, 45067 Orléans, FranceInstitut de Chimie Organique et Analytique ICOA, CNRS UMR 7311, Université d’Orléans, 45067 Orléans, FranceDepartment of Analytical Chemistry, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 16 University Street, 700115 Iasi, RomaniaDepartment of Analytical Chemistry, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 16 University Street, 700115 Iasi, RomaniaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 16 University Street, 700115 Iasi, RomaniaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 16 University Street, 700115 Iasi, RomaniaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 16 University Street, 700115 Iasi, RomaniaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 16 University Street, 700115 Iasi, RomaniaStarting from indomethacin (IND), one of the most prescribed non-steroidal anti-inflammatory drugs (NSAIDs), new nitric oxide-releasing indomethacin derivatives with 1,3,4-oxadiazole-2-thiol scaffold (NO-IND-OXDs, <b>8a–p</b>) have been developed as a safer and more efficient multitarget therapeutic strategy. The successful synthesis of designed compounds (intermediaries and finals) was proved by complete spectroscopic analyses. In order to study the in silico interaction of NO-IND-OXDs with cyclooxygenase isoenzymes, a molecular docking study, using AutoDock 4.2.6 software, was performed. Moreover, their biological characterization, based on in vitro assays, in terms of thermal denaturation of serum proteins, antioxidant effects and the NO releasing capacity, was also performed. Based on docking results, <b>8k, 8l</b> and <b>8m</b> proved to be the best interaction for the COX-2 (cyclooxygense-2) target site, with an improved docking score compared with celecoxib. Referring to the thermal denaturation of serum proteins and antioxidant effects, all the tested compounds were more active than IND and aspirin, used as references. In addition, the compounds <b>8c</b>, <b>8h</b>, <b>8i</b>, <b>8m</b>, <b>8n</b> and <b>8o</b> showed increased capacity to release NO, which means they are safer in terms of gastrointestinal side effects.https://www.mdpi.com/1422-0067/22/13/7079indomethacin1,3,4-oxadiazole-2-thiolnitric oxidedocking studycyclooxygenaseinflammation |
| spellingShingle | Alexandru Sava Frederic Buron Sylvain Routier Alina Panainte Nela Bibire Sandra Mădălina Constantin Florentina Geanina Lupașcu Alin Viorel Focșa Lenuţa Profire Design, Synthesis, In Silico and In Vitro Studies for New Nitric Oxide-Releasing Indomethacin Derivatives with 1,3,4-Oxadiazole-2-thiol Scaffold International Journal of Molecular Sciences indomethacin 1,3,4-oxadiazole-2-thiol nitric oxide docking study cyclooxygenase inflammation |
| title | Design, Synthesis, In Silico and In Vitro Studies for New Nitric Oxide-Releasing Indomethacin Derivatives with 1,3,4-Oxadiazole-2-thiol Scaffold |
| title_full | Design, Synthesis, In Silico and In Vitro Studies for New Nitric Oxide-Releasing Indomethacin Derivatives with 1,3,4-Oxadiazole-2-thiol Scaffold |
| title_fullStr | Design, Synthesis, In Silico and In Vitro Studies for New Nitric Oxide-Releasing Indomethacin Derivatives with 1,3,4-Oxadiazole-2-thiol Scaffold |
| title_full_unstemmed | Design, Synthesis, In Silico and In Vitro Studies for New Nitric Oxide-Releasing Indomethacin Derivatives with 1,3,4-Oxadiazole-2-thiol Scaffold |
| title_short | Design, Synthesis, In Silico and In Vitro Studies for New Nitric Oxide-Releasing Indomethacin Derivatives with 1,3,4-Oxadiazole-2-thiol Scaffold |
| title_sort | design synthesis in silico and in vitro studies for new nitric oxide releasing indomethacin derivatives with 1 3 4 oxadiazole 2 thiol scaffold |
| topic | indomethacin 1,3,4-oxadiazole-2-thiol nitric oxide docking study cyclooxygenase inflammation |
| url | https://www.mdpi.com/1422-0067/22/13/7079 |
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