title: Synthesis and cytotoxicity of new platinum(IV) complexes of mixed carboxylates.
abstract: In order to develop new antitumor platinum(IV) complexes with highly tuned lipophilicity, a series of (diamine)Pt(IV) complexes of the formula [Pt(IV)(dach)L(3)L'] or [Pt(IV)(dach)L(2)L"(2)] (dach=trans-(+/-)-1,2-diaminocyclohexane; L=acetato, propionato; L'=acetato, propionato, valerato or pivalato; L"=trifluoroacetato) have been synthesized by electrophilic substitution of the tris(carboxylato)hydroxoplatinum(IV) complexes, [Pt(IV)(dach)L(3)OH] (L=acetato, propionato), with various carboxylic anhydrides such as acetic, trifluoroacetic, pivalic and valeric anhydrides. The present platinum(IV) complexes were fully characterized by means of elemental analyses, 1H NMR, mass and IR spectroscopies. The complexes 8 and 10, satisfying the appropriate range of lipophilicity (logP=0.18-1.54), exhibited high activity (ED(50), 5.1 and 1.3 microM, respectively) compared with other complexes, which implies that the lipophilicity is an important factor for the antitumor activity of this series of complexes.
authors.affiliation: Life Sciences Division, Korea Institute of Science and Technology, 136-791, Seoul, South Korea.
authors.forename: Rita
authors.initials: R
authors.lastname: Song
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Park
authors.forename: Yeong Sang
authors.initials: YS
authors.lastname: Kim
authors.forename: Youngmee
authors.initials: Y
authors.lastname: Kim
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Byung Tae
authors.initials: BT
authors.lastname: Ahn
authors.forename: Youn Soo
authors.initials: YS
authors.lastname: Sohn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D006157:Guanosine Monophosphate / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D010984:Platinum / Q000737:chemistry*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D009942:Organometallic Compounds; D010984:Platinum; D006157:Guanosine Monophosphate