Synthesis of new multitarget-directed ligands containing thienopyrimidine nucleus for inhibition of 15-lipoxygenase, cyclooxygenases, and pro-inflammatory cytokines.

ABSTRACT: A new series of thieno[2,3-d]pyrimidine derivatives 4, 5, 6a-o, and 11 was designed and synthesized starting from cyclohexanone under Gewald condition with the aim to develop multitarget-directed ligands (MTDLs) having anti-inflammatory properties against both 15-LOX and COX-2 enzymes. Moreover, the potential of the compounds against the proinflammatory mediators NO, ROS, TNF-α, and IL-6 were tested in LPS-activated RAW 264.7 macrophages. Compound 6o showed the greatest 15-LOX inhibitory effect (IC₅₀ = 1.17 μM) which was superior to that of the reference nordihydroguaiaretic acid (NDGA, IC₅₀ = 1.28 μM); meanwhile, compounds 6h, 6g, 11, and 4 exhibited potent activities (IC₅₀ = 1.29-1.77 μM). The ester 4 (SI = 137.37) and the phenyl-substituted acetohydrazid

SUBMITTER: Abdelkhalek AS 

PROVIDER: S-EPMC10247423 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature