Synthesis, Structural Characterization, and Pro‐apoptotic Activity of 1‐Indanone Thiosemicarbazone Platinum(II) and Palladium(II) Complexes: Potential as Antileukemic Agents

Abstract

In the search for alternative chemotherapeutic strategies against leukemia, various 1-indanone thiosemicarbazones, as well as eight novel platinum(II) and palladium(II) complexes, with the formula [MCl₂(HL)] and [M(HL)(L)]Cl, derived from two 1-indanone thiosemicarbazones were synthesized and tested for antiproliferative activity against the human leukemia U937 cell line. The crystal structure of [Pt(HL1)(L1)]Cl·2MeOH, where L1=1-indanone thiosemicarbazone, was solved by X-ray diffraction. Free thiosemicarbazone ligands showed no antiproliferative effect, but the corresponding platinum(II) and palladium(II) complexes inhibited cell proliferation and induced apoptosis. Platinum(II) complexes also displayed selective apoptotic activity in U937 cells but not in peripheral blood monocytes or the human hepatocellular carcinoma HepG2 cell line used to screen for potential hepatotoxicity. Present findings show that, in U937 cells, 1-indanone thiosemicarbazones coordinated to palladium(II) were more cytotoxic than those complexed with platinum(II), although the latter were found to be more selective for leukemic cells suggesting that they are promising compounds with potential therapeutic application against hematological malignancies.

Activity on Trypanosoma cruzi, erythrocytes lysis and biologically relevant physicochemical properties of Pd(II) and Pt(II) complexes of thiosemicarbazones derived from 1-indanones

“…The (Table 2), similarly to previously reported for the Pt complex [29]. The Pd\N bond distances are significantly different, 2.064(2) Å and 2.118(2) Å; this feature was not seen in the Pt complex because of its higher standard deviations that made Pt\N bond lengths indistinguishable.…”

“…1, compounds 3-6) were synthesized by ligand substitution on Na 2 [PdCl 4 ] or K 2 [PtCl 4 ], using a 1:1 metal to ligand molar ratio as previously reported [29]. [M(HL)(L)]Cl complexes ( Fig.…”

“…[M(HL)(L)]Cl complexes ( Fig. 1, compounds 7-10) were synthesized by ligand substitution on the same precursors, but using a 1:2 metal to ligand molar ratio [29].…”

“…1, compounds 3-10) and L = 1-indanone containing thiosemicarbazones 1 and 2 ( Fig. 1) [29]. The eight metal compounds showed antiproliferative activity against the human leukemia U937 cell line.…”

“…The eight metal compounds showed antiproliferative activity against the human leukemia U937 cell line. Platinum (II) complexes displayed selective apoptotic activity in U937 cells but not in peripheral blood monocytes or the human hepatocellular carcinoma HepG2 cell line used to screen for potential hepatotoxicity, suggesting that they are promising compounds with potential therapeutic application against hematological malignancies [29]. Metabolic pathways of Trypanosoma parasites are supposed to be similar to those present in tumor cells and other highly proliferative cells, leading in many cases to a correlation between antitrypanosomal and antitumor activities [18,30].…”