Phytocompounds in Precision Dermatology: COX-2 Inhibitors as a Therapeutic Target in Atopic-Prone Skin
Atopic dermatitis (AD) is a chronic, multifactorial inflammatory skin disease characterized by persistent pruritus, immune system dysregulation, and an increased expression of cyclooxygenase-2 (COX-2), an enzyme that plays a central role in the production of prostaglandins and the promotion of infla...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/15/7/998 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1839616333885472768 |
|---|---|
| author | Muhammad Suleman Abrar Mohammad Sayaf Chiara Moltrasio Paola Maura Tricarico Francesco Giambuzzi Erika Rimondi Elisabetta Melloni Paola Secchiero Annalisa Marcuzzi Angelo Valerio Marzano Sergio Crovella |
| author_facet | Muhammad Suleman Abrar Mohammad Sayaf Chiara Moltrasio Paola Maura Tricarico Francesco Giambuzzi Erika Rimondi Elisabetta Melloni Paola Secchiero Annalisa Marcuzzi Angelo Valerio Marzano Sergio Crovella |
| author_sort | Muhammad Suleman |
| collection | DOAJ |
| description | Atopic dermatitis (AD) is a chronic, multifactorial inflammatory skin disease characterized by persistent pruritus, immune system dysregulation, and an increased expression of cyclooxygenase-2 (COX-2), an enzyme that plays a central role in the production of prostaglandins and the promotion of inflammatory responses. In this study, we employed a comprehensive computational pipeline to identify phytocompounds capable of inhibiting COX-2 activity, offering an alternative to traditional non-steroidal anti-inflammatory drugs. The African and Traditional Chinese Medicine natural product databases were subjected to molecular screening, which identified six top compounds, namely, Tophit1 (−16.528 kcal/mol), Tophit2 (−10.879 kcal/mol), Tophit3 (−9.760 kcal/mol), Tophit4 (−9.752 kcal/mol), Tophit5 (−8.742 kcal/mol), and Tophit6 (−8.098 kcal/mol), with stronger binding affinities to COX-2 than the control drug rofecoxib (−7.305 kcal/mol). Molecular dynamics simulations over 200 ns, combined with MM/GBSA binding free energy calculations, consistently identified Tophit1 and Tophit2 as the most stable complexes, exhibiting exceptional structural integrity and a strong binding affinity to the target protein. ADMET profiling via SwissADME and pkCSM validated the drug-likeness, oral bioavailability, and safety of the lead compounds, with no Lipinski rule violations and favorable pharmacokinetic and toxicity profiles. These findings underscore the therapeutic potential of the selected phytocompounds as novel COX-2 inhibitors for the management of atopic-prone skin and warrant further experimental validation. |
| format | Article |
| id | doaj-art-1ec524713a9f4c738adb041d0e6d82b8 |
| institution | Matheson Library |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-1ec524713a9f4c738adb041d0e6d82b82025-07-25T13:16:31ZengMDPI AGBiomolecules2218-273X2025-07-0115799810.3390/biom15070998Phytocompounds in Precision Dermatology: COX-2 Inhibitors as a Therapeutic Target in Atopic-Prone SkinMuhammad Suleman0Abrar Mohammad Sayaf1Chiara Moltrasio2Paola Maura Tricarico3Francesco Giambuzzi4Erika Rimondi5Elisabetta Melloni6Paola Secchiero7Annalisa Marcuzzi8Angelo Valerio Marzano9Sergio Crovella10Laboratory of Animal Research Center (LARC), Qatar University, Doha P.O. Box 2713, QatarSchool of Chemical Sciences, University Sains Malaysia, Gelugor 11800, MalaysiaDermatology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, ItalyDepartment of Pediatrics, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, 34137 Trieste, ItalyDepartment of Advanced Diagnostics, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, 34137 Trieste, ItalyDepartment of Translational Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyDermatology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, ItalyDepartment of Biomedical Sciences, Health Cluster, Qatar University, Doha P.O. Box 2713, QatarAtopic dermatitis (AD) is a chronic, multifactorial inflammatory skin disease characterized by persistent pruritus, immune system dysregulation, and an increased expression of cyclooxygenase-2 (COX-2), an enzyme that plays a central role in the production of prostaglandins and the promotion of inflammatory responses. In this study, we employed a comprehensive computational pipeline to identify phytocompounds capable of inhibiting COX-2 activity, offering an alternative to traditional non-steroidal anti-inflammatory drugs. The African and Traditional Chinese Medicine natural product databases were subjected to molecular screening, which identified six top compounds, namely, Tophit1 (−16.528 kcal/mol), Tophit2 (−10.879 kcal/mol), Tophit3 (−9.760 kcal/mol), Tophit4 (−9.752 kcal/mol), Tophit5 (−8.742 kcal/mol), and Tophit6 (−8.098 kcal/mol), with stronger binding affinities to COX-2 than the control drug rofecoxib (−7.305 kcal/mol). Molecular dynamics simulations over 200 ns, combined with MM/GBSA binding free energy calculations, consistently identified Tophit1 and Tophit2 as the most stable complexes, exhibiting exceptional structural integrity and a strong binding affinity to the target protein. ADMET profiling via SwissADME and pkCSM validated the drug-likeness, oral bioavailability, and safety of the lead compounds, with no Lipinski rule violations and favorable pharmacokinetic and toxicity profiles. These findings underscore the therapeutic potential of the selected phytocompounds as novel COX-2 inhibitors for the management of atopic-prone skin and warrant further experimental validation.https://www.mdpi.com/2218-273X/15/7/998atopic dermatitisCOX-2phytocompoundsmolecular dynamics simulationpharmacokineticstoxicity |
| spellingShingle | Muhammad Suleman Abrar Mohammad Sayaf Chiara Moltrasio Paola Maura Tricarico Francesco Giambuzzi Erika Rimondi Elisabetta Melloni Paola Secchiero Annalisa Marcuzzi Angelo Valerio Marzano Sergio Crovella Phytocompounds in Precision Dermatology: COX-2 Inhibitors as a Therapeutic Target in Atopic-Prone Skin Biomolecules atopic dermatitis COX-2 phytocompounds molecular dynamics simulation pharmacokinetics toxicity |
| title | Phytocompounds in Precision Dermatology: COX-2 Inhibitors as a Therapeutic Target in Atopic-Prone Skin |
| title_full | Phytocompounds in Precision Dermatology: COX-2 Inhibitors as a Therapeutic Target in Atopic-Prone Skin |
| title_fullStr | Phytocompounds in Precision Dermatology: COX-2 Inhibitors as a Therapeutic Target in Atopic-Prone Skin |
| title_full_unstemmed | Phytocompounds in Precision Dermatology: COX-2 Inhibitors as a Therapeutic Target in Atopic-Prone Skin |
| title_short | Phytocompounds in Precision Dermatology: COX-2 Inhibitors as a Therapeutic Target in Atopic-Prone Skin |
| title_sort | phytocompounds in precision dermatology cox 2 inhibitors as a therapeutic target in atopic prone skin |
| topic | atopic dermatitis COX-2 phytocompounds molecular dynamics simulation pharmacokinetics toxicity |
| url | https://www.mdpi.com/2218-273X/15/7/998 |
| work_keys_str_mv | AT muhammadsuleman phytocompoundsinprecisiondermatologycox2inhibitorsasatherapeutictargetinatopicproneskin AT abrarmohammadsayaf phytocompoundsinprecisiondermatologycox2inhibitorsasatherapeutictargetinatopicproneskin AT chiaramoltrasio phytocompoundsinprecisiondermatologycox2inhibitorsasatherapeutictargetinatopicproneskin AT paolamauratricarico phytocompoundsinprecisiondermatologycox2inhibitorsasatherapeutictargetinatopicproneskin AT francescogiambuzzi phytocompoundsinprecisiondermatologycox2inhibitorsasatherapeutictargetinatopicproneskin AT erikarimondi phytocompoundsinprecisiondermatologycox2inhibitorsasatherapeutictargetinatopicproneskin AT elisabettamelloni phytocompoundsinprecisiondermatologycox2inhibitorsasatherapeutictargetinatopicproneskin AT paolasecchiero phytocompoundsinprecisiondermatologycox2inhibitorsasatherapeutictargetinatopicproneskin AT annalisamarcuzzi phytocompoundsinprecisiondermatologycox2inhibitorsasatherapeutictargetinatopicproneskin AT angelovaleriomarzano phytocompoundsinprecisiondermatologycox2inhibitorsasatherapeutictargetinatopicproneskin AT sergiocrovella phytocompoundsinprecisiondermatologycox2inhibitorsasatherapeutictargetinatopicproneskin |