Synthesis, antitumor activity, and molecular docking study of 2-cyclopentyloxyanisole derivatives: mechanistic study of enzyme inhibition.

ABSTRACT: A series of 24 compounds was synthesised based on a 2-cyclopentyloxyanisole scaffold 3-14 and their in vitro antitumor activity was evaluated. Compounds 4a, 4b, 6b, 7b, 13, and 14 had the most potent antitumor activity (IC₅₀ range: 5.13-17.95 μM), compared to those of the reference drugs celecoxib, afatinib, and doxorubicin. The most active derivatives 4a, 4b, 7b, and 13 were evaluated for their inhibitory activity against COX-2, PDE4B, and TNF-α. Compounds 4a and 13 potently inhibited TNF-α (IC₅₀ values: 2.01 and 6.72 μM, respectively) compared with celecoxib (IC₅₀=6.44 μM). Compounds 4b and 13 potently inhibited COX-2 (IC₅₀ values: 1.08 and 1.88 μM, respectively) comparable to that of celecoxib (IC₅₀=0.68 μM). Compounds 4a, 7b, and 13 inhibited PDE4B (IC₅₀ values: 5.62, 5.65, and 3.98 μM, respectively) compared with the reference drug roflumilast (IC₅₀=1.55 μM). The molecular docking of compounds 4b and 13 with the COX-2 and PDE4B binding pockets was studied.HighlightsAntitumor activity of new synthesized cyclopentyloxyanisole scaffold was evaluated.The powerful antitumor 4a, 4b, 6b, 7b & 13 were assessed as COX-2, PDE4B & TNF-α inhibitors.Compounds 4a, 7b, and 13 exhibited COX-2, PDE4B, and TNF-α inhibition.Compounds 4b and 13 showed strong interactions at the COX-2 and PDE4B binding pockets.

SUBMITTER: El-Husseiny WM 

PROVIDER: S-EPMC7144195 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature