title: Synthesis and evaluation of thalidomide and phthalimide esters as antitumor agents.
abstract: A series of thalidomide and phthalimide ester analogs were efficiently synthesized from N-chloromethylthalidomide, N-chloromethylphthalimide, and N-(2-bromoethyl)phthalimide derivatives with various biologically important carboxylic acids. The synthesized compounds were purified and characterized by various chromatographic and spectroscopic techniques. The antitumor activity of all the synthesized compounds was screened against human liver and breast cancer cells, which showed that phthalimide ester 6a was the best cytotoxic compound against MCF7 cells, while all of the tested compounds showed a non-cytotoxic effect against HepG2 cells. Compounds 5a, 6a, and 7a possess immunosuppressant effect, while compounds 5c, 5d, 6c, 6d, 7c, and 7d showed an immunostimmulatory effect. Meanwhile, estimation of the binding affinity for all the synthesized compounds toward the vascular endothelial growth factor receptor (VEGFR) showed that compounds 5a, 5b, and 7d were the most potent inhibitors.
authors.affiliation: Faculty of Science, Department of Chemistry, Menoufia University, Shebin El-Koam, Egypt.
authors.forename: Magdy A H
authors.initials: MA
authors.lastname: Zahran
authors.forename: Yasmin G
authors.initials: YG
authors.lastname: Abdin
authors.forename: Amany M A
authors.initials: AM
authors.lastname: Osman
authors.forename: Amira M
authors.initials: AM
authors.lastname: Gamal-Eldeen
authors.forename: Roba M
authors.initials: RM
authors.lastname: Talaat
authors.forename: Erik B
authors.initials: EB
authors.lastname: Pedersen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004952:Esters; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D015394:Molecular Structure; D010797:Phthalimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004952:Esters; D010797:Phthalimides; C037431:phthalimide; D013792:Thalidomide; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Antitumor; Esters; Phthalimide; Thalidomide; VEGFR