Design, synthesis, and molecular modeling of heterocyclic bioisostere as potent PDE4 inhibitors.

Autor: Almatary AM; Faculty of Pharmacy, Department of Pharmaceutical Organic Chemistry, Mansoura University, Mansoura, Egypt.; Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Horus University, New Damietta, Egypt., Elmorsy MA; Faculty of Pharmacy, Department of Pharmaceutical Organic Chemistry, Mansoura University, Mansoura, Egypt., El Husseiny WM; Faculty of Pharmacy, Department of Pharmaceutical Organic Chemistry, Mansoura University, Mansoura, Egypt., Selim KB; Faculty of Pharmacy, Department of Pharmaceutical Organic Chemistry, Mansoura University, Mansoura, Egypt., El-Sayed MA; Faculty of Pharmacy, Department of Pharmaceutical Organic Chemistry, Mansoura University, Mansoura, Egypt.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2018 Apr; Vol. 351 (3-4), pp. e1700403. Date of Electronic Publication: 2018 Mar 24.
DOI: 10.1002/ardp.201700403
Abstrakt: 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.
(© 2018 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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