Studies on two new mixed ligand platinum compounds with a trans-geometry.
In this paper we report the synthesis and in vitro activity of two new mixed ligand platinum complexes: trans-[PtCl₂(thiazole)(imidazole) [JH3] and trans-[PtCl₂(thiazole)(3-hydroxypyridine) [JH4]. Although the compounds are less active than cisplatin against the parent ovarian cancer cell line A2780, they are more active than cisplatin against the resistant cell lines A2780(cisR) and A2780(ZD0473R), thus indicating that JH3 and JH4 have been better able to overcome mechanisms of resistance operating in A2780(cisR) and A2780(ZD0473R). When Pt-DNA binding levels at 24 h in A2780, A2780(cisR) and A2780(ZD0473R) cell lines are compared it is found that whereas for cisplatin the values in resistant cell lines are significantly lower than that in the parent cell line, for JH3 and JH4 Pt-DNA binding levels in the parent and resistant cell lines are comparable, thus providing an explanation for variations in activity of the compounds in the three cell lines.
Discipline of Biomedical Science, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. fazlul.huq@sydney.edu.au.
Jehad
J
Al-Shuneigat
Jun Qing
JQ
Yu
Philip
P
Beale
Keith
K
Fisher
Fazlul
F
Huq
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D008024:Ligands; D009944:Organoplatinum Compounds; D002945:Cisplatin