Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Design, synthesis and biological evaluation of novel pyridine derivatives as anticancer agents and phosphodiesterase 3 inhibitors
Bioorganic and Medicinal Chemistry, Volume 17, No. 16, Year 2009
Notification
URL copied to clipboard!
Description
Two series of 4,6-diaryl-2-imino-1,2-dihydropyridine-3-carbonitriles and their isosteric 4,6-diaryl-2-oxo-1,2-dihydropyridine-3-carbonitriles were synthesized through a combinatorial approach. The prepared analogues were evaluated for their in vitro capacity to inhibit PDE3A and the growth of the human HT-29 colon adenocarcinoma tumor cell line. Compound 6-(4-bromophenyl)-4-(2-ethoxyphenyl)-2-imino-1,2-dihydropyridine-3-carbo nitrile (Id) exhibited the strongest PDE3 inhibition when cGMP but not cAMP is the substrate with a IC50of 27 μM, which indicates a highly selective mechanism of enzyme inhibition. On the other hand, compound 6-(1,3-benzodioxol-5-yl)-4-(2-ethoxyphenyl)-2-imino-1,2-dihydropyridine- 3-carbonitrile (Ii) was the most active in inhibiting colon tumor cell growth with a IC50 of 3 μM. The electronic effects, steric effects and conformational aspects of Id seem to be the most crucial for the PDE3 inhibition. Meanwhile, steric factors and the H-bonding capability seem to be the most important factors for tumor cell growth inhibitory activity. Conversely, there is no direct correlation between PDE3 inhibition and anticancer activity for the prepared compounds. An in silico docking experiment indicates the potential involvement of other potential molecular targets such as PIM-1 kinase to explain its tumor cell growth inhibitory activity. © 2009 Elsevier Ltd.
Authors & Co-Authors
Abadi, Ashraf Hassan
Egypt, New Cairo
Faculty of Pharmacy and Biotechnology
Ibrahim, Tamer M.
Egypt, New Cairo
Faculty of Pharmacy and Biotechnology
Abouzid, Khaled Abouzid Mohamed
Egypt, Cairo
Faculty of Pharmacy - Ain Shams University
Lehmann, Jochen
Germany, Jena
Friedrich-schiller-universität Jena
Tinsley, Heather Nicole
United States, Birmingham
Southern Research
Gary, Bernard D.
United States, Birmingham
Southern Research
Piazza, Gary A.
United States, Birmingham
Southern Research
Statistics
Citations: 84
Authors: 7
Affiliations: 4
Identifiers
Doi:
10.1016/j.bmc.2009.06.063
ISSN:
09680896
Research Areas
Cancer
Study Approach
Quantitative