Cellular Pharmacology of Palladinum(III) Hematoporphyrin IX Complexes: Solution Stability, Antineoplastic and Apoptogenic Activity, DNA Binding, and Processing of DNA-Adducts.

Two paramagnetic Pd complexes of hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp), namely a dinuclear one [Pd₂(Hp)Cl₃(H₂O)₅]·2PdCl₂, and a mononuclear metalloporphyrin type [Pd(Hp)Cl(H₂O)]·H₂O, have been synthesized reproducibly and isolated as neutral compounds at different reaction conditions. Their structure and solution stability have been assayed by UV/Vis and EPR spectroscopy. The compounds researched have shown in vitro cell growth inhibitory effects at micromolar concentration against a panel of human tumor cell lines. A DNA fragmentation test in the HL-60 cell line has indicated that causes comparable proapoptotic effects with regard to cisplatin but at substantially higher concentrations. and cisplatin form intra-strand guanine bis-adducts as the palladium complex is less capable of forming DNA adducts. This demonstrates its cisplatin-dissimilar pharmacological profile. The test for efficient removal of DNA-adducts by the NER synthesis after modification of pBS plasmids with either cisplatin or has manifested that the lesions induced by cisplatin are far better recognized and repaired compared those of . The study on the recognition and binding of the HMGB-1 protein to cisplatin or modified DNA probes have shown that HMG proteins are less involved in the palladium agent cytotoxicity.