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 (IC 50 range: 5.13-17.95 lM), 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-a. Compounds 4a and 13 potently inhibited TNF-a (IC 50 values: 2.01 and 6.72 lM, respectively) compared with celecoxib (IC 50 ¼6.44 lM). Compounds 4b and 13 potently inhibited COX-2 (IC 50 values: 1.08 and 1.88 lM, respectively) comparable to that of celecoxib (IC 50 ¼0.68 lM). Compounds 4a, 7b, and 13 inhibited PDE4B (IC 50 values: 5.62, 5.65, and 3.98 lM, respectively) compared with the reference drug roflumilast (IC 50 ¼1.55 lM). The molecular docking of compounds 4b and 13 with the COX-2 and PDE4B binding pockets was studied. HIGHLIGHTS Antitumor activity of new synthesized cyclopentyloxyanisole scaffold was evaluated. The powerful antitumor 4a, 4b, 6b, 7b & 13 were assessed as COX-2, PDE4B & TNF-a inhibitors. Compounds 4a, 7b, and 13 exhibited COX-2, PDE4B, and TNF-a inhibition. Compounds 4b and 13 showed strong interactions at the COX-2 and PDE4B binding pockets.

An Investigation into the Interaction between Double Hydroxide-Based Antioxidant Benzophenone Derivatives and Cyclooxygenase 2

“…It appears that all of the three compounds have the capability to occupy the upper part of the aforementioned hydrophobic channel between Arg120 and near Tyr385 [34,35]. Compounds of this type can be hopeful COX2 inhibitors [36,37]. The molecular interaction of the most active compounds DB2, SC2 and YB2, with the COX2 enzyme was further validated by fluorescence spectral studies.…”

Prospects of Topoisomerase Inhibitors as Promising Anti-Cancer Agents

“…TOPO II is an enzyme that recognizes specific DNA sequences, usually regions with double-stranded DNA, during its mechanism of action (MOA) [22]. It cleaves both strands As a result, a covalent phosphotyrosine bond is formed that binds the protein to the freshly generated 5' end of the DNA chain [27,28]. Simultaneously, a 3'-hydroxyl group is generated on the opposite end of the cleaved strand.…”

Antiproliferative Activity, Multikinase Inhibition, Apoptosis- Inducing Effects and Molecular Docking of Novel Isatin–Purine Hybrids

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