In vitro pharmacological study of monomeric platinum(III) hematoporphyrin IX complexes

Three stable mononuclear hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp) complexes of Pt^III, namely cis-[ Pt^III(NH₃)₂(Hp_−3H)(H₂O)₂].H₂O 1, [Pt^III(Hp_−3H)(H₂O)₂].H₂O 2 and [Pt^III((O,O)Hp_−2H)Cl(H₂O)₃] 3 with distorted octahedral structure and (d_z2)¹ ground state have been tested in vitro for antineoplastic activity in a panel of tumor cell lines. The novel platinum(III) complexes showed cytotoxic activity in a concentration-dependent manner with IC₅₀ values comparable to those of referent cytotoxic agent cisplatin together with lower cytotoxicity against renal cells. Further detailed evaluation of the active analogue 2 and the less active complex 3 showed that their potency greatly correlates with the ability to induce apoptosis and to bind DNA. Despite the structural dissimilarities between complex 2 and cisplatin, their DNA-adducts were equally effectively recognized and repaired by the nucleotide excision repair system. Complex 2 showed quite superior ability to accumulate in K-562 cells relative to cisplatin.