Potent Anticancer Activity and Possible Low Toxicity of Platinum(II) Complexes with Functionalized 1,1‐Cyclobutanedicarboxylate as a Leaving Ligand

Abstract

Two platinum(II) complexes, DN603 and DN604, were designed and prepared by using 3-oxocyclobutane-1,1-dicarboxylate as a ligand. The compounds were prepared according to the concept that incorporation of a functionalized moiety in the leaving ligand that did not affect its coordination bonding to the metal atom would play a key role in the anticancer activity of the resulting platinum complex. The newly prepared compounds were found to show potent in vitro anticancer activity comparable to cisplatin and oxaliplatin; especially DN604, which exhibited low acute toxicity similar to carboplatin, and presented acceptable solubility and stability in water. Chemical and biological results indicated that the functionalized moiety, uncoordinated, led to potent anticancer activity and low apparent toxicity of the platinum complexes by affecting the kinetic properties of the compounds.

Hybrid of DNA-targeting Chlorambucil with Pt(IV) Species to Reverse Drug Resistance

“…Materials and General Measurements. Common chemicals and solvents were purchased from Sinopharm Chemical Reagent Co.(Beijing, China) DN604 (1) and DN603 (2) were prepared as described previously (Zhao et al, 2014). Elemental analyses for C, H, and N were done on a Vario MICRO CHNOS Elemental Analyzer (Elementar, Fulda, Germany).…”

“…As a result, the leaving ligand plays a significant role in determining the toxicity and side effects of a platinum drug. With the purpose of retaining the advantage of 1,1-cyclobutanedicarboxylate as a leaving ligand and also improving the kinetic properties of the resulting platinum complexes, we have introduced a carbonyl group to the skeleton of 1,1-cyclobutanedicarboxylate, in which the functionalized moiety (carbonyl group) could achieve the desired balance between hydrophilicity and lipophilicity of the resulting platinum complex and may improve the kinetic properties as well as the DNA-binding ability of the derivatives (Zhao et al, 2014). Such platinum complexes, named DN603 and DN604 (Fig.…”

Isomeric Effect on the Pharmacokinetic Behavior of Anticancer CuII Mixed Chelate Complexes: Experimental and Theoretical Approach

“…CasIII-La CasIII-Ea Cisplatin [34] Carboplatin [31] Lobaplatin LP-D1 [35] Lobaplatin LP-D2 [35] Dose [mg kg [8] -0.806 [8] -2.19 [51] -2.3 [51] 1.48 [56] 1.48 [56] Parameter SM54111 [36] DN604 [32] Dicycloplatin [37] LCC0601 (S,S) [38] LCC0601 (R,R) [38] Oxaliplatin [53] Dose [55] ----1.65 [51] Figure 3. Pt compounds presented in Table 3: (1) cisplatin, (2) carboplatin, (3) dicycloplatin, (4) lobaplatin LP-D1, (5) lobaplatin LP-D2, (6) SM54111, (7) LLC0601 (R,R), (8) LLC0601 (S,S), (9) DN604, and (10) oxaliplatin.…”

Improving the anticancer activity of platinum(iv) prodrugs using a dual-targeting strategy with a dichloroacetate axial ligand

“…[15][16][17][18] In our previous research, complexes A and B exhibited similar activity compared with cisplatin and oxaliplatin, but their toxicity against normal cells was lower than that of cisplatin and oxaliplatin. 19,20 The results indicated that both of them were promising anticancer lead compounds for further study (Fig. 1).…”

“…Molecular formulas and [M + Na] + experimental and theoretical of 1a-2b Creative Commons Attribution-NonCommercial 3.0 Unported Licence.study 19. All tumor cell lines were purchased from Hangzhou Hibio bioTech company.…”