title: Novel C,N-chelate platinum(II) antitumor complexes bearing a lipophilic ethisterone pendant.
abstract: The novel steroidal carrier ligand 17-α-[4'-ethynyl-dimethylbenzylamine]-17-β-testosterone (ET-dmba 1) and the steroid--C,N-chelate platinum(II) derivatives [Pt(ET-dmba)Cl(L)] (L = DMSO (2) and PTA (3; PTA =1,3,5-triaza-7-phosphaadamantane)) have been prepared. Values of IC(50) were calculated for the new platinum complexes 2 and 3 against a panel of human tumor cell lines representative of ovarian (A2780 and A2780cisR) and breast cancers (T47D). At 48h incubation time complexes 2 and 3 show very low resistance factors (RF of <2) against an A2780 cell line which has acquired resistant to cisplatin and were more active than cisplatin (about 4-fold for 3) in T47D (AR+, AR=androgen receptor). Compound 1 retains a moderate degree of relative binding affinity (RBA=0.94%) for androgen receptors. The cytotoxicity of the non steroidal platinum analogues [Pt(dmba)Cl(L)] (dmba=dimethylbenzylamine; L=DMSO (4) and PTA (5)) has also been studied for comparison purposes. Theoretical calculations at the BP86/def2-TZVP level of theory on complex 3 have been undertaken.
authors.affiliation: Departamento de Química Inorgánica, Universidad de Murcia, Campus de Espinardo, Murcia, Spain. jruiz@um.es
authors.forename: José
authors.initials: J
authors.lastname: Ruiz
authors.forename: Venancio
authors.initials: V
authors.lastname: Rodríguez
authors.forename: Natalia
authors.initials: N
authors.lastname: Cutillas
authors.forename: Arturo
authors.initials: A
authors.lastname: Espinosa
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hannon
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005003:Ethisterone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C560081:17-(4'-ethynyldimethylbenzylamine)-17-testosterone; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D005003:Ethisterone