title: Novel quinazolin-4(3H)-one/Schiff base hybrids as antiproliferative and phosphodiesterase 4 inhibitors: design, synthesis, and docking studies.
abstract: A novel series of quinazolin-4(3H)-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 IC50 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 IC50 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.
authors.affiliation: Faculty of Pharmacy, Medicinal Chemistry Department, Assiut University, Assiut, Egypt.
authors.forename: Hamdy M
authors.initials: HM
authors.lastname: Abdel-Rahman
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Aziz
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Canzoneri
authors.forename: Bernard D
authors.initials: BD
authors.lastname: Gary
authors.forename: Gary A
authors.initials: GA
authors.lastname: Piazza
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012545:Schiff Bases / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D058988:Phosphodiesterase 4 Inhibitors; D052999:Quinazolinones; D012545:Schiff Bases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4
keywords: Antiproliferative; Docking; Hybrids; PDE4B inhibitors; Quinazolin-4(3H)-one