Novel Derivatives of Eugenol as a New Class of PPARγ Agonists in Treating Inflammation: Design, Synthesis, SAR Analysis and In Vitro Anti-Inflammatory Activity
The main objective of this research was to develop novel compounds from readily accessed natural products especially eugenol with potential biological activity. Eugenol, the principal chemical constituent of clove (<i>Eugenia caryophyllata</i>) from the family Myrtaceae is renowned for i...
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MDPI AG
2023-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/9/3899 |
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| author | Noor Fathima Anjum Dhivya Shanmugarajan B. R. Prashantha Kumar Syed Faizan Priya Durai Ruby Mariam Raju Saleem Javid Madhusudan N. Purohit |
| author_facet | Noor Fathima Anjum Dhivya Shanmugarajan B. R. Prashantha Kumar Syed Faizan Priya Durai Ruby Mariam Raju Saleem Javid Madhusudan N. Purohit |
| author_sort | Noor Fathima Anjum |
| collection | DOAJ |
| description | The main objective of this research was to develop novel compounds from readily accessed natural products especially eugenol with potential biological activity. Eugenol, the principal chemical constituent of clove (<i>Eugenia caryophyllata</i>) from the family Myrtaceae is renowned for its pharmacological properties, which include analgesic, antidiabetic, antioxidant, anticancer, and anti-inflammatory effects. According to reports, PPARγ regulates inflammatory reactions. The synthesized compounds were structurally analyzed using FT-IR, <sup>1</sup>HNMR, <sup>13</sup>CNMR, and mass spectroscopy techniques. Molecular docking was performed to analyze binding free energy and important amino acids involved in the interaction between synthesized derivatives and the target protein. The development of the structure–activity relationship is based on computational studies. Additionally, the stability of the best-docked protein–ligand complexes was assessed using molecular dynamic modeling. The in-vitro PPARγ competitive binding Lanthascreen TR-FRET assay was used to confirm the affinity of compounds to the target protein. All the synthesized derivatives were evaluated for an in vitro anti-inflammatory activity using an albumin denaturation assay and HRBC membrane stabilization at varying concentrations from 6.25 to 400 µM. In this background, with the aid of computational research, we were able to design six novel derivatives of eugenol synthesized, analyzed, and utilized TR-FRET competitive binding assay to screen them for their ability to bind PPARγ. Anti-inflammatory activity evaluation through in vitro albumin denaturation and HRBC method revealed that <b>1f</b> exhibits maximum inhibition of heat-induced albumin denaturation at 50% and 85% protection against HRBC lysis at 200 and 400 µM, respectively. Overall, we found novel derivatives of eugenol that could potentially reduce inflammation by PPARγ agonism. |
| first_indexed | 2024-03-11T04:11:53Z |
| format | Article |
| id | doaj.art-20b51c7c9171415caf68c0380042a41d |
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| language | English |
| last_indexed | 2024-03-11T04:11:53Z |
| publishDate | 2023-05-01 |
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| series | Molecules |
| spelling | doaj.art-20b51c7c9171415caf68c0380042a41d2023-11-17T23:24:58ZengMDPI AGMolecules1420-30492023-05-01289389910.3390/molecules28093899Novel Derivatives of Eugenol as a New Class of PPARγ Agonists in Treating Inflammation: Design, Synthesis, SAR Analysis and In Vitro Anti-Inflammatory ActivityNoor Fathima Anjum0Dhivya Shanmugarajan1B. R. Prashantha Kumar2Syed Faizan3Priya Durai4Ruby Mariam Raju5Saleem Javid6Madhusudan N. Purohit7Department of Pharmaceutical Chemistry, Farooqia College of Pharmacy, Mysuru 570 015, IndiaDepartment of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570 015, IndiaDepartment of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570 015, IndiaDepartment of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570 015, IndiaDepartment of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570 015, IndiaDepartment of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570 015, IndiaDepartment of Pharmaceutical Chemistry, Farooqia College of Pharmacy, Mysuru 570 015, IndiaDepartment of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570 015, IndiaThe main objective of this research was to develop novel compounds from readily accessed natural products especially eugenol with potential biological activity. Eugenol, the principal chemical constituent of clove (<i>Eugenia caryophyllata</i>) from the family Myrtaceae is renowned for its pharmacological properties, which include analgesic, antidiabetic, antioxidant, anticancer, and anti-inflammatory effects. According to reports, PPARγ regulates inflammatory reactions. The synthesized compounds were structurally analyzed using FT-IR, <sup>1</sup>HNMR, <sup>13</sup>CNMR, and mass spectroscopy techniques. Molecular docking was performed to analyze binding free energy and important amino acids involved in the interaction between synthesized derivatives and the target protein. The development of the structure–activity relationship is based on computational studies. Additionally, the stability of the best-docked protein–ligand complexes was assessed using molecular dynamic modeling. The in-vitro PPARγ competitive binding Lanthascreen TR-FRET assay was used to confirm the affinity of compounds to the target protein. All the synthesized derivatives were evaluated for an in vitro anti-inflammatory activity using an albumin denaturation assay and HRBC membrane stabilization at varying concentrations from 6.25 to 400 µM. In this background, with the aid of computational research, we were able to design six novel derivatives of eugenol synthesized, analyzed, and utilized TR-FRET competitive binding assay to screen them for their ability to bind PPARγ. Anti-inflammatory activity evaluation through in vitro albumin denaturation and HRBC method revealed that <b>1f</b> exhibits maximum inhibition of heat-induced albumin denaturation at 50% and 85% protection against HRBC lysis at 200 and 400 µM, respectively. Overall, we found novel derivatives of eugenol that could potentially reduce inflammation by PPARγ agonism.https://www.mdpi.com/1420-3049/28/9/3899eugenol derivativesmolecular dockingpharmacophorestructure–activity relationshipanti-inflammatory activity |
| spellingShingle | Noor Fathima Anjum Dhivya Shanmugarajan B. R. Prashantha Kumar Syed Faizan Priya Durai Ruby Mariam Raju Saleem Javid Madhusudan N. Purohit Novel Derivatives of Eugenol as a New Class of PPARγ Agonists in Treating Inflammation: Design, Synthesis, SAR Analysis and In Vitro Anti-Inflammatory Activity Molecules eugenol derivatives molecular docking pharmacophore structure–activity relationship anti-inflammatory activity |
| title | Novel Derivatives of Eugenol as a New Class of PPARγ Agonists in Treating Inflammation: Design, Synthesis, SAR Analysis and In Vitro Anti-Inflammatory Activity |
| title_full | Novel Derivatives of Eugenol as a New Class of PPARγ Agonists in Treating Inflammation: Design, Synthesis, SAR Analysis and In Vitro Anti-Inflammatory Activity |
| title_fullStr | Novel Derivatives of Eugenol as a New Class of PPARγ Agonists in Treating Inflammation: Design, Synthesis, SAR Analysis and In Vitro Anti-Inflammatory Activity |
| title_full_unstemmed | Novel Derivatives of Eugenol as a New Class of PPARγ Agonists in Treating Inflammation: Design, Synthesis, SAR Analysis and In Vitro Anti-Inflammatory Activity |
| title_short | Novel Derivatives of Eugenol as a New Class of PPARγ Agonists in Treating Inflammation: Design, Synthesis, SAR Analysis and In Vitro Anti-Inflammatory Activity |
| title_sort | novel derivatives of eugenol as a new class of pparγ agonists in treating inflammation design synthesis sar analysis and in vitro anti inflammatory activity |
| topic | eugenol derivatives molecular docking pharmacophore structure–activity relationship anti-inflammatory activity |
| url | https://www.mdpi.com/1420-3049/28/9/3899 |
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