1. Academic Validation
  2. Synthesis, in vivo anti-inflammatory, COX-1/COX-2 and 5-LOX inhibitory activities of new 2,3,4-trisubstituted thiophene derivatives

Synthesis, in vivo anti-inflammatory, COX-1/COX-2 and 5-LOX inhibitory activities of new 2,3,4-trisubstituted thiophene derivatives

  • Bioorg Chem. 2020 Sep;102:103890. doi: 10.1016/j.bioorg.2020.103890.
Nermeen A Qandeel 1 Ashraf K El-Damasy 2 Maha H Sharawy 3 Said M Bayomi 1 Nadia S El-Gohary 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
  • 2 Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: ph_karem2000@mans.edu.eg.
  • 3 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
  • 4 Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: dr.nadiaelgohary@yahoo.com.
Abstract

New series of thiophene derivatives were synthesized and evaluated for their in vivo anti-inflammatory activity using carrageenan-induced paw edema model. The most active in vivo anti-inflammatory compounds 5b, 11b, 14c, 18c, 19c and 20d were further evaluated for their in vitro COX-1/COX-2 and 5-LOX inhibitory activities. The in vitro assay results revealed that the N-(4-(4-chlorophenyl)-3-cyanothiophen-2-yl)-2-morpholinoacetamide (5b) possesses the highest selectivity toward COX-2 (IC50 = 5.45 μM) with selectivity index value of 8.37 compared to celecoxib with COX-2 selectivity index value of 15.44. In addition, it showed acceptable 5-LOX inhibitory activity (IC50 = 4.33 μM) compared to NDGA (IC50 = 2.46 μM). Molecular modeling study was conducted to study the postulated binding of compound 5b into the active site of COX-2 and 5-LOX, and it revealed that 5b binds similarly to celecoxib and NDGA, respectively. Overall, the morpholinoacetamide-thiophene hybrid 5b could serve as a promising lead for further development of new potent anti-inflammatory agents that act as dual COX-2/5-LOX inhibitors.

Keywords

5-LOX; Anti-inflammatory; COX-1/COX-2; Molecular modeling; Thiophenes.

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