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Design, synthesis, and molecular modeling of heterocyclic bioisostere as potent PDE4 inhibitors
Author(s) -
Almatary Aya M.,
Elmorsy Mohammad A.,
El Husseiny Walaa M.,
Selim Khalid B.,
ElSayed Magda A.A.
Publication year - 2018
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201700403
Subject(s) - roflumilast , bioisostere , chemistry , apoptosis , cell cycle , structure–activity relationship , phosphodiesterase , stereochemistry , chemical synthesis , combinatorial chemistry , biochemistry , enzyme , in vitro , psychology , psychiatry , copd
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.