title: Design, synthesis and bioevaluation of novel maleamic amino acid ester conjugates of 3,5-bisarylmethylene-4-piperidones as cytostatic agents.
abstract: A novel series of maleamic amino acid ester conjugates of 3,5-bisarylmethylene-4-piperidones were prepared to investigate the efficacy of micronutrient conjugation in enhancing cytotoxic potency by improving selectivity and delivery. These compounds, prepared as anticancer agents, were expected to demonstrate enhanced selectivity towards malignant cells through the inhibition of topoisomerase IIalpha via protein thiolation. The cytostatic effects of these compounds were evaluated against three cell lines, namely murine L1210 leukemia cells, human Molt 4/C8 and CEM T-lymphocyte cells. All compounds were found to have greater potency than the reference drug melphalan. Several compounds were found to potently inhibit topoisomerase IIalpha and displayed cytostatic activity in the nanomolar range.
authors.affiliation: Département des Sciences, Université Sainte-Anne, Pointe-de-l'Eglise, NE, Canada BOW1MO.
authors.forename: Dani
authors.initials: D
authors.lastname: Youssef
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Potter
authors.forename: Mamta
authors.initials: M
authors.lastname: Jha
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: James P
authors.initials: JP
authors.lastname: Stables
authors.forename: Amitabh
authors.initials: A
authors.lastname: Jha
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D018360:Crystallography, X-Ray; D054697:Cytostatic Agents / Q000494:pharmacology*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000627:therapeutic use; D006367:HeLa Cells; D006801:Humans; D007939:Leukemia L1210; D051379:Mice; D010881:Piperidones / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D054697:Cytostatic Agents; D004952:Esters; D010881:Piperidones