Synthesis and characterization of Pd(II) and Pt(II) complexes of p-isopropylbenzaldehyde N-protected thiosemicarbazones. Cytotoxic activity against ras-transformed cells.
Cytotoxicity tests in tumor cells sensitive to cis-DDP (HL-60, JURKAT, Hela and 3T3) and in tumor cells transformed by ras oncogenes and resistant to cis-DDP (Pam 212-ras) show that cyclometallated complexes 1a [Pd(p-is.TSCN-NHMe)]4, 2b [Pt(p-is.TSCN-NMe2)]4 and 4a [Pd(p-is.TSCN-NHex)]4 may be endowed with specific cytotoxic properties. In fact, these three novel metal-thiosemicarbazone compounds kill Pam 212-ras cells through apoptosis induction. These results, together with others recently published, indicate that the design and synthesis of metallated-thiosemicarbazone compounds may lead to the discovery of novel antitumor agents able to circumvent cis-DDP resistance, in particular tumor cell lines.
Quiroga
A G
AG
Departamento de Química Inorgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
Pérez
J M
JM
Montero
E I
EI
West
D X
DX
Alonso
C
C
Navarro-Ranninger
C
C
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D011905:Genes, ras / Q000187:drug effects; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D010984:Platinum; D010165:Palladium; C111909:4-isopropylbenzaldehyde thiosemicarbazone