Technical Field
The present disclosure relates to platinum(II) complexes with antiproliferative or antitumor activities. More specifically, these platinum(II) complexes are platinum(II)-chlorides having selones as co-ligands.
Description of the Related Art
The “background” description provided herein is for the purpose of generally presenting the context of the disclosure. All references cited herein are incorporated by reference. Work of the presently named inventors, to the extent it is described in this background section, as well as aspects of the description which may not otherwise qualify as prior art at the time of filing, are neither expressly or impliedly admitted as prior art against the present disclosure.
Since the approval of cisplatin for clinical use to treat cancer in 1978, platinum compounds continue to be among the most efficient anticancer drugs available [Johnstone et al. Chem. Rev., 2016, 116, 3436-3486; Shahana Dilruba and, Ganna V. Kalayda, Cancer Chemotherapy and Pharmacology, 2016, 77 (6), pg. 1103-1124; Wheate et al, 2010; 39: 8113-8127; Medici et al. Chem. Rev. 284 (2015) 329-350; Wang et al. Chem. Soc. Rev., (2013) 42: 202-224; Jung et al. Chem. Rev. 107 (2007) 1387-1407; Wong et al. Nature Rev. Drug Disc. 4 (2005) 307-320; Kelland, L. (2007) Nature Reviews Cancer, 7: 573-584; Jan Reedijk, Eur. J. Inorg. Chem. 2009, 1303-1312; and Dasari et al. Eur. J. Pharmacol. 2014, 364-378.]. Despite the wide spectrum of anticancer activity shown by the platinum compounds their therapeutic efficacy is somewhat compromised by the occurrence of serious side effects [Dasari et al. Eur. J. Pharmacol. 2014, 364-378; Florea et al. Cancers 2011, 3, 1351-1371 (toxicity); Hartmann et al. (2003) 4, 889-901; and Piccolini et al. Cell Biol Toxicol (2013) 29:339-353] and development of resistance [Galluzzi et al. Oncogene (2012) 31, 1869-1883; D. J. Stewart, Crit. Rev. Oncol. Hematol. 63 (2007) 12-31; and Zisowsky et al. Biochem. Pharmacol. 2007, 73, 298]. The ability of platinum complexes to significantly inhibit tumor growth is a direct result of their reaction with nuclear DNA [Chaney et al. Crit. Rev. Oncol. Hematol. 53 (2005) 3-11; Zutphen et al. Coord. Chem. Rev. 249 (2005) 2845-2853; Jamieson et al. (1999). Chemical Reviews, 99: 2467-2498; Ahmad et al. Transition Metal Chemistry (2006) 31, 1003-1016; S. Ahmad, Chemistry & Biodiversity 7 (2010) 543-566; Fuertes et al. Curr. Med. Chem. (2003) 10, 257; and Komeda, S. (2011) Metallomics, 3: 650-655.]. However, prior to binding to DNA, aquation of the drug is required [Ahmad et al. (2006) and Ahmad et al. (2010)]. Aquation is usually the rate-determining step in the reaction of platinum(II) complexes with DNA [Knox et al. Cancer Res., 46, 1972 (1986]. Due to the low concentration of chloride, cisplatin undergoes aquation inside the cell and is converted to the highly reactive species [Pt(NH3)2Cl(H2O)]+, which forms mainly 1,2-GpG intrastrand adducts with DNA. Adduct formation leads to inhibition of transcription and replication of DNA, and ultimately to tumor cell apoptosis. Carboplatin displays a mode of action similar to that of cisplatin, but it is less reactive than cisplatin [Mlcouskova et al. J Biol Inorg Chem (2012) 17:891-898]. The rate of aquation of the leaving group of carboplatin, namely the 1,1 cyclobutanedicarboxylate ligand, is nearly half of cisplatin. Consequently, carboplatin is used at higher dosage and has fewer side effects compared to cisplatin during clinical treatment [Boulikas et al. Oncol. Rep. 10 (2003) 1663]. The strong and irreversible binding of cisplatin to intracellular thiolate ligands is believed to deactivate the drug by preventing it from reaching the biological target, DNA. Sulfur containing biomolecules such as cysteine, methionine, and glutathione have high affinity for platinum(II) complexes and ligate rapidly to Pt+2 ions that enter the cell [Ahmad (2006); J. Reedijk, Chem. Rev. 1999, 99, 2499; and J. Reedijk, Chem. Commun. 1996, 801]. This preferential binding of platinum to sulfur donors rather than the bases of DNA causes resistance to cisplatin [Galluzzi et al. (2012), Stewart (2007), Liu et al. J. Inorg. Biochem. 2004, 98, 702; and Messori et al. Coord. Chem. Rev., 315 (2016) 67-89].
In view of the forgoing, one object of the present disclosure is to provide a new class of platinum(II) complexes having cytotoxic properties against cancer and/or tumors with reduced side effects.
USPTO Backgrounds
USPTO Backgrounds