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Novel Quinazolin‐4(3 H )‐one/Schiff Base Hybrids as Antiproliferative and Phosphodiesterase 4 Inhibitors: Design, Synthesis, and Docking Studies
Author(s) -
AbdelRahman Hamdy M.,
AbdelAziz Mohamed,
Canzoneri Joshua C.,
Gary Bernard D.,
Piazza Gary A.
Publication year - 2014
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.201400083
Subject(s) - phosphodiesterase , chemistry , docking (animal) , stereochemistry , combinatorial chemistry , schiff base , biochemistry , pharmacology , enzyme , biology , medicine , nursing
A novel series of quinazolin‐4(3 H )‐one/Schiff base hybrids was rationally designed and synthesized. The prepared compounds were evaluated for in vitro activity to inhibit phosphodiesterase 4 (PDE4), where several of them showed good‐to‐moderate activity compared to rolipram. Compound 7 showed potent PDE4 inhibition in this series, with an IC 50 of 1.60 µM. Compounds that showed PDE4 inhibition were further assessed for antiproliferative activity using different human tumor cell lines. Compound 10 exhibited significant antiproliferative activity with IC 50 values of 140, 79, and 320 nM in breast, lung, and colon tumor cells, respectively. Docking of compound 7 in the active site of PDE4B illustrates its possible binding mode and provides insight for further optimizations of this novel scaffold for inhibiting PDE4.