title: A convenient synthesis and molecular modeling study of novel purine and pyrimidine derivatives as CDK2/cyclin A3 inhibitors.
abstract: A series of novel purine and pyrimidine derivatives were prepared and biologically evaluated for their in vitro anti-CDK2/cyclin A3 and antitumor activities in Ehrlich ascites carcinoma (EAC) cell based assay. The novel purine derivatives 13a,b demonstrated potent inhibitor activities with IC(50) values of 14±9 and 13±9 μM, respectively. Additionally, compound 15a showed the highest potency (IC(50)=10±6 μM) in EAC cell based assay. Molecular modeling study, including fitting to a 3D-pharmacophore model and their docking into cyclin dependant kinase2 (CDK2) active site showed high fit values and docking scores.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Ain Shams, Abbassia 11566, Cairo, Egypt. aselgazwy@yahoo.com
authors.forename: Abdel-Sattar S Hamad
authors.initials: AS
authors.lastname: Elgazwy
authors.forename: Nasser S M
authors.initials: NS
authors.lastname: Ismail
authors.forename: Heba S A
authors.initials: HS
authors.lastname: Elzahabi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D003198:Computer Simulation; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011687:Purines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D000970:Antineoplastic Agents; D051357:Cyclin-Dependent Kinase 2; D047428:Protein Kinase Inhibitors; D011687:Purines; D011743:Pyrimidines; D013449:Sulfonamides; C555726:N-(((1,2-dicyano-2-(((4-methoxyphenyl)methylene)amino)vinyl)amino)carbonyl)-4-methylbenzenesulfonamide; D000096926:Benzenesulfonamides