In vivo analgesic, anti-inflammatory and molecular docking studies of S-naproxen derivatives
Naveed Muhammad,
Rashid Khan,
Faiza Seraj,
Abad Khan,
Ubaid Ullah,
Abdul Wadood,
Amar Ajmal,
Uzma,
Basharat Ali,
Khalid Mohammed Khan,
Noor Ul Ain Nawaz,
Najla AlMasoud,
Taghrid S. Alomar,
Abdur Rauf
Affiliations
Naveed Muhammad
Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakhtunkhwa, Pakistan; Corresponding author. Department of Chemistry, University of Swabi, Swabi, 23430, Pakistan.
Rashid Khan
Department of Pharmacy, University of Swabi, Swabi, Khyber Pakhtunkhwa, Pakistan
Faiza Seraj
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
Abad Khan
Department of Pharmacy, University of Swabi, Swabi, Khyber Pakhtunkhwa, Pakistan
Ubaid Ullah
Department of Pharmacy, University of Swabi, Swabi, Khyber Pakhtunkhwa, Pakistan
Abdul Wadood
Department of Biochemistry, Abdul Wali Khan University, Mardan, Pakhtunkhwa, Pakistan
Amar Ajmal
Department of Biochemistry, Abdul Wali Khan University, Mardan, Pakhtunkhwa, Pakistan
Uzma
Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakhtunkhwa, Pakistan
Basharat Ali
Sulaiman Bin Abdullah Aba Al-Khail (SA)- Center for Interdisciplinary Research in Basic Science, International Islamic University, Islamabad, Pakistan
Khalid Mohammed Khan
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan; Pakistan Academy of Science, 3-Constitution Avenue, G-5/2, Islamabad, 44000, Pakistan; Corresponding author. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
Noor Ul Ain Nawaz
Department of Pharmacy, City University of Science and Information Technology Peshawar, Peshawar, Khyber Pakhtunkhwa, Pakistan
Najla AlMasoud
Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84427, Riyadh, 11671, Saudi Arabia
Taghrid S. Alomar
Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84427, Riyadh, 11671, Saudi Arabia
Abdur Rauf
Department of Chemistry, University of Swabi, Swabi, 23430, Pakistan; Corresponding author. Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakhtunkhwa, Pakistan.
In the current studies two naproxen derivatives (NPD) were evaluated for analgesic and anti-inflammatory properties. The acetic acid and hot plate animal models were used to screen the compounds for analgesic potential. While the anti-inflammatory potential was evaluated through animal paw edema, induced by several inflammatory mediators (carrageenan, bradykinin, and prostaglandin E2), the xylene-induced ear edema was also used as an inflammatory model. Both NPDs showed significant (p < 0.001) antinociceptive effects in the acetic acid-induced writhing paradigm. In the case of the hot plate, the NPD 1 at the tested dose of 5 mg/kg enhanced the latency time after 60 min of injection, which remained significant (p < 0.001) up to the end of the experiment duration. The maximum percent inhibition of NPD 1 was 87.53. The naloxone injection significantly lowered the latency time of NPD 1 as compared to NPD 2. Regarding the anti-inflammatory effect, both of the tested NPDs demonstrated a significant reduction in paw edema against various inflammatory mediators, as mentioned above; however, the anti-inflammatory effect of NPD 1 was better. The maximal percent inhibition by NPD 1 and 2 was 43.24 (after 60 min) and 45.93 (after 90 min). A considerable effect also resulted from xylene-induced ere edema. Further, a molecular docking study was carried out to investigate the binding modes of the NPD. The docking analysis revealed that the NPD significantly interacted with the COX2 enzyme. Furthermore, molecular dynamics simulation was carried out for the docked complexes. The MD simulation analysis revealed the high stability of the two naproxen derivatives.
