67387-76-2Relevant articles and documents
Synthesis, antitumor activity, and molecular docking study of 2-cyclopentyloxyanisole derivatives: mechanistic study of enzyme inhibition
Abdel-Aziz, Alaa A.-M.,AlSaif, Nawaf A.,Alanazi, Mohammed M.,El-Azab, Adel S.,El-Husseiny, Walaa M.,El-Sayed, Magda A.-A.
, p. 744 - 758 (2020)
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.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-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.
Design, synthesis, and molecular modeling of heterocyclic bioisostere as potent PDE4 inhibitors
Almatary, Aya M.,Elmorsy, Mohammad A.,El Husseiny, Walaa M.,Selim, Khalid B.,El-Sayed, Magda A.-A.
, (2018)
A new hybrid template was designed by combining the structural features of phosphodiesterase 4 (PDE4) inhibitors with several heterocyclic moieties which present an integral part in the skeleton of many apoptotic agents. Thirteen compounds of the synthesized hybrids displayed higher inhibitory activity against PDE4B than the reference drug, roflumilast. Further investigation indicated that compounds 13b and 20 arrested the cell cycle at the G2/M phase and the pre-G1 phase, and induced cell death by apoptosis of A549 cells in a caspase-dependent manner.
Comparison of the full-length and 152~528 truncate of human cyclic nucleotide phosphodiesterase 4b2 for the characterization of inhibitors
Zhang, Xiang,He, Shu,Hu, Xiaolei,Wu, Jing,Li, Xinpeng,Liao, Fei,Yang, Xiaolan
, p. 49 - 58 (2019/08/06)
Aim and Objective: Human full-length cyclic nucleotide phosphodiesterase isozyme 4B2 (hPDE4B2) as the target for screening and characterizing inhibitors suffers from low activity yield and the coexistence of two conformational states bearing different aff
