Discover natural compounds as potential phosphodiesterase-4B inhibitors via computational approaches

Jing Li, Nan Zhou, Wen Liu, Jianzong Li, Yu Feng, Xiaoyun Wang, Chuanfang Wu, Jinku Bao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


cAMP, intracellular cyclic adenosine monophosphate, is a ubiquitous second messenger that plays a key role in many physiological processes. PDE4B which can reduce the cAMP level by hydrolyzing cAMP to 5′-AMP has become a therapeutic target for the treatment of human diseases such as respiratory disorders, inflammation diseases, neurological and psychiatric disorders. However, the use of currently available PDE4B inhibitors is restricted due to serious side effects caused by targeting PDE4D. Hence, we are attempting to find out subfamily-selective PDE4B inhibitors from natural products, using computer-aided approaches such as virtual screening, docking, and molecular dynamics simulation. Finally, four potential PDE4B-selective inhibitors (ZINC67912770, ZINC67912780, ZINC72320169, and ZINC28882432) were found. Compared to the reference drug (roflumilast), they scored better during the virtual screening process. Binding free energy for them was-317.51,-239.44,-215.52, and-165.77 kJ/mol, better than-129.05 kJ/mol of roflumilast. The pharmacophore model of the four candidate inhibitors comprised six features, including one hydrogen bond donor, four hydrogen bond acceptors, and one aromatic ring feature. It is expected that our study will pave the way for the design of potent PDE4B-selective inhibitors of new drugs to treat a wide variety of diseases such as asthma, COPD, psoriasis, depression, etc.

Original languageEnglish
Pages (from-to)1101-1112
Number of pages12
JournalJournal of Biomolecular Structure and Dynamics
Issue number5
Publication statusPublished - 3 May 2016
Externally publishedYes


  • cAMP
  • phosphodiesterase-4B
  • inhibitor
  • drug development
  • in silico


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