title: Novel piperidinedione analogs as inhibitors of breast cancer cell growth.
abstract: We previously reported the utility of antineoplaston-A10 (3-phenylacetylamino-2,6-piperidinedione) as an endogenous cancer protector and immune modulator in breast cancer patients (Cancer Lett., 2000, 157, 57). In this study, four new piperidinedione A10 analogs were synthesized and tested for their antimitotic activity on a human breast cancer cell line against the prototype A10 and the antibreast cancer drug tamoxifen. Moreover, the DNA binding capacity of such compounds was evaluated against A10, (E)-3-(4-Nitrocinnamoylamino)-2,6-piperidinedione "3B" and (E)-3-(4-hydroxycinnamoylamino)-2,6-piperidinedione "3D" were several-fold more potent antiproliferative agents than A10 and tamoxifen. They also had significantly higher capacity to bind DNA than A10. Conversely, (E)-3-(cinnamoylamino)-2,6-piperidinedione "3A" and (E)-3-(4-methoxycinnamoylamino)-2,6-piperidinedione) "3C" had weaker biological profiles than the lead compound A10. Detailed synthetic, spectroscopic, and biological data are reported.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: L A
authors.initials: LA
authors.lastname: Abou-Zeid
authors.forename: A M
authors.initials: AM
authors.lastname: el-Mowafy
authors.forename: M B
authors.initials: MB
authors.lastname: el-Ashmawy
authors.forename: L B
authors.initials: LB
authors.lastname: Hendry
authors.forename: A M
authors.initials: AM
authors.lastname: Abdelal
authors.forename: F A
authors.initials: FA
authors.lastname: Badria
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D044482:Benzeneacetamides; D004273:DNA, Neoplasm / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D010881:Piperidones / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D044482:Benzeneacetamides; D004273:DNA, Neoplasm; D010881:Piperidones; C052091:antineoplaston A10