Synthesis and cytotoxicity of new platinum(IV) complexes of mixed carboxylates.
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.
Song
Rita
R
Life Sciences Division, Korea Institute of Science and Technology, 136-791, Seoul, South Korea.
Park
Sun Young
SY
Kim
Yeong Sang
YS
Kim
Youngmee
Y
Kim
Sung Jin
SJ
Ahn
Byung Tae
BT
Sohn
Youn Soo
YS
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
D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D009942:Organometallic Compounds; D010984:Platinum; D006157:Guanosine Monophosphate