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Monofunctional Platinum-containing Pyridine-based Ligand Acts Synergistically in Combination with the Phytochemicals Curcumin and Quercetin in Human Ovarian Tumour Models.

With the idea that platinum compounds that bind with DNA differently than cisplatin may be better-able to overcome platinum resistance in ovarian tumor, the monofunctional platinum complex tris(imidazo(1,2-α)pyridine) chloroplatinum(II) chloride (coded as LH6) has been synthesized and investigated for its activity, alone and in combination with the phytochemicals curcumin and quercetin, against human ovarian A2780, A2780(cisR) and A2780(ZD0473R) cancer cell lines. LH6 is found to be more active than cisplatin against the resistant cell lines and its bolus combinations with curcumin and quercetin are found to produce more pronounced cell kill. Whereas platinum accumulation from cisplatin is found to increase almost linearly with time, that from LH6 reaches a maximum at 4 h and is somewhat lowered at 24 h. It is possible that the presence of bulky hydrophobic imidazo (1,2-α-pyridine) ligand in LH6 facilitates its rapid uptake through the cytoplasmic membrane. Lower platinum accumulation at 24 h than at 4 h for LH6 can be seen to imply that efflux processes may be more dominant as the period of incubation is increased. When platinum-DNA binding levels at 24 h are compared, cisplatin is found to be associated with the higher level in the parent A2780 cell line and LH6 in the resistant A2780(cisR) cell line, in line with greater activity of cisplatin in the parent cell line and that of LH6 in the resistant cell line. If the observed in vitro activity of LH6 is confirmed in vivo, it can be seen to have the potential for development as novel platinum based anticancer drug.