Exploring the potential of propanamide-sulfonamide based drug conjugates as dual inhibitors of urease and cyclooxygenase-2: biological and their in silico studies
Derivative synthesis has been a crucial method for altering the effects of already-approved medications, especially to lessen adverse effects and enhance results. Making use of this multi-target approach, a series of naproxen-sulfa drug conjugates was designed and synthesized. The newly designed con...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-08-01
|
| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2023.1206380/full |
| _version_ | 1797755576663408640 |
|---|---|
| author | Saghir Ahmad Saghir Ahmad Muhammad Abdul Qadir Mahmood Ahmed Muhammad Imran Numan Yousaf Tanveer A. Wani Seema Zargar Ijaz Ali Muhammad Muddassar |
| author_facet | Saghir Ahmad Saghir Ahmad Muhammad Abdul Qadir Mahmood Ahmed Muhammad Imran Numan Yousaf Tanveer A. Wani Seema Zargar Ijaz Ali Muhammad Muddassar |
| author_sort | Saghir Ahmad |
| collection | DOAJ |
| description | Derivative synthesis has been a crucial method for altering the effects of already-approved medications, especially to lessen adverse effects and enhance results. Making use of this multi-target approach, a series of naproxen-sulfa drug conjugates was designed and synthesized. The newly designed conjugates were confirmed by spectroscopic techniques like IR, 1HNMR, 13CNMR, and elemental analysis. The conjugates were screened for anti-inflammatory, urease, and cyclooxygenase-2 (COX-2) inhibition. Naproxen conjugated with sulfanilamide, sulfathiazole, and sulfaguanidine was found potent and showed a competitive mode of urease inhibition, with IC50 (µM) values 6.69 ± 0.11, 5.82 ± 0.28, 5.06 ± 0.29, respectively. When compared to other screened conjugates, the naproxen-sulfamethoxazole conjugation showed better anti-inflammatory action by inhibiting induced edema by 82.8%, which is comparable to the medication indomethacin (86.8% inhibition). Whereas it exhibited 75.4% inhibition of COX-2 at 10 µM concentration which is comparable with the reference drug (celecoxib, 77.1% inhibition). Moreover, the binding modes of competitive inhibitors with the urease and COX-2 receptor were predicted through molecular docking studies and their stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and there were no conformational changes that occurred during simulation. The obtained results showed that the conjugates of approved therapeutic molecules may lead to the development of novel types of pharmacological agents in the treatment of several pathological disorders where urease and COX-2 enzymes are involved. |
| first_indexed | 2024-03-12T17:48:15Z |
| format | Article |
| id | doaj.art-183b37fcd32748f38800b435d11d24e1 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-03-12T17:48:15Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-183b37fcd32748f38800b435d11d24e12023-08-03T10:02:47ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462023-08-011110.3389/fchem.2023.12063801206380Exploring the potential of propanamide-sulfonamide based drug conjugates as dual inhibitors of urease and cyclooxygenase-2: biological and their in silico studiesSaghir Ahmad0Saghir Ahmad1Muhammad Abdul Qadir2Mahmood Ahmed3Muhammad Imran4Numan Yousaf5Tanveer A. Wani6Seema Zargar7Ijaz Ali8Muhammad Muddassar9School of Chemistry, University of the Punjab, Lahore, PakistanDepartment of Microbiology, Immunology and Cancer Biology, School of Medicine, University of Virginia, Charlottesville, VA, United StatesSchool of Chemistry, University of the Punjab, Lahore, PakistanDepartment of Chemistry, Division of Science and Technology, University of Education, Lahore, PakistanKAM School of Life Sciences, FC College (A Chartered University), Lahore, PakistanDepartment of Biosciences, COMSATS University Islamabad, Islamabad, PakistanDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Biochemistry, College of Science, King Saud University, Riyadh, Saudi ArabiaCenter for Applied Mathematics and Bioinformatics, Gulf University for Science and Technology, Kuwait City, KuwaitDepartment of Biosciences, COMSATS University Islamabad, Islamabad, PakistanDerivative synthesis has been a crucial method for altering the effects of already-approved medications, especially to lessen adverse effects and enhance results. Making use of this multi-target approach, a series of naproxen-sulfa drug conjugates was designed and synthesized. The newly designed conjugates were confirmed by spectroscopic techniques like IR, 1HNMR, 13CNMR, and elemental analysis. The conjugates were screened for anti-inflammatory, urease, and cyclooxygenase-2 (COX-2) inhibition. Naproxen conjugated with sulfanilamide, sulfathiazole, and sulfaguanidine was found potent and showed a competitive mode of urease inhibition, with IC50 (µM) values 6.69 ± 0.11, 5.82 ± 0.28, 5.06 ± 0.29, respectively. When compared to other screened conjugates, the naproxen-sulfamethoxazole conjugation showed better anti-inflammatory action by inhibiting induced edema by 82.8%, which is comparable to the medication indomethacin (86.8% inhibition). Whereas it exhibited 75.4% inhibition of COX-2 at 10 µM concentration which is comparable with the reference drug (celecoxib, 77.1% inhibition). Moreover, the binding modes of competitive inhibitors with the urease and COX-2 receptor were predicted through molecular docking studies and their stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and there were no conformational changes that occurred during simulation. The obtained results showed that the conjugates of approved therapeutic molecules may lead to the development of novel types of pharmacological agents in the treatment of several pathological disorders where urease and COX-2 enzymes are involved.https://www.frontiersin.org/articles/10.3389/fchem.2023.1206380/fullsulfonamidesNSAIDsureaseinflammationcyclooxygenase-2in-silico studies |
| spellingShingle | Saghir Ahmad Saghir Ahmad Muhammad Abdul Qadir Mahmood Ahmed Muhammad Imran Numan Yousaf Tanveer A. Wani Seema Zargar Ijaz Ali Muhammad Muddassar Exploring the potential of propanamide-sulfonamide based drug conjugates as dual inhibitors of urease and cyclooxygenase-2: biological and their in silico studies Frontiers in Chemistry sulfonamides NSAIDs urease inflammation cyclooxygenase-2 in-silico studies |
| title | Exploring the potential of propanamide-sulfonamide based drug conjugates as dual inhibitors of urease and cyclooxygenase-2: biological and their in silico studies |
| title_full | Exploring the potential of propanamide-sulfonamide based drug conjugates as dual inhibitors of urease and cyclooxygenase-2: biological and their in silico studies |
| title_fullStr | Exploring the potential of propanamide-sulfonamide based drug conjugates as dual inhibitors of urease and cyclooxygenase-2: biological and their in silico studies |
| title_full_unstemmed | Exploring the potential of propanamide-sulfonamide based drug conjugates as dual inhibitors of urease and cyclooxygenase-2: biological and their in silico studies |
| title_short | Exploring the potential of propanamide-sulfonamide based drug conjugates as dual inhibitors of urease and cyclooxygenase-2: biological and their in silico studies |
| title_sort | exploring the potential of propanamide sulfonamide based drug conjugates as dual inhibitors of urease and cyclooxygenase 2 biological and their in silico studies |
| topic | sulfonamides NSAIDs urease inflammation cyclooxygenase-2 in-silico studies |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2023.1206380/full |
| work_keys_str_mv | AT saghirahmad exploringthepotentialofpropanamidesulfonamidebaseddrugconjugatesasdualinhibitorsofureaseandcyclooxygenase2biologicalandtheirinsilicostudies AT saghirahmad exploringthepotentialofpropanamidesulfonamidebaseddrugconjugatesasdualinhibitorsofureaseandcyclooxygenase2biologicalandtheirinsilicostudies AT muhammadabdulqadir exploringthepotentialofpropanamidesulfonamidebaseddrugconjugatesasdualinhibitorsofureaseandcyclooxygenase2biologicalandtheirinsilicostudies AT mahmoodahmed exploringthepotentialofpropanamidesulfonamidebaseddrugconjugatesasdualinhibitorsofureaseandcyclooxygenase2biologicalandtheirinsilicostudies AT muhammadimran exploringthepotentialofpropanamidesulfonamidebaseddrugconjugatesasdualinhibitorsofureaseandcyclooxygenase2biologicalandtheirinsilicostudies AT numanyousaf exploringthepotentialofpropanamidesulfonamidebaseddrugconjugatesasdualinhibitorsofureaseandcyclooxygenase2biologicalandtheirinsilicostudies AT tanveerawani exploringthepotentialofpropanamidesulfonamidebaseddrugconjugatesasdualinhibitorsofureaseandcyclooxygenase2biologicalandtheirinsilicostudies AT seemazargar exploringthepotentialofpropanamidesulfonamidebaseddrugconjugatesasdualinhibitorsofureaseandcyclooxygenase2biologicalandtheirinsilicostudies AT ijazali exploringthepotentialofpropanamidesulfonamidebaseddrugconjugatesasdualinhibitorsofureaseandcyclooxygenase2biologicalandtheirinsilicostudies AT muhammadmuddassar exploringthepotentialofpropanamidesulfonamidebaseddrugconjugatesasdualinhibitorsofureaseandcyclooxygenase2biologicalandtheirinsilicostudies |