Exploring the Anticancer Potential of Diiron Bis-cyclopentadienyl Complexes with Bridging Hydrocarbyl Ligands: Behavior in Aqueous Media and In Vitro Cytotoxicity

Abstract

A series of diiron complexes based on the [Fe2Cp2(CO) x ] skeleton (Cp = η5-C5H5, x = 2, 3; η4-C5H5Ph in place of one Cp in one case) and containing different bridging hydrocarbyl ligands (aminocarbyne, thiocarbyne, allenyl) were preliminarily investigated for their anticancer potential. The water solubility, stability in water and in the presence of a cell culture medium, and octanol/water partition coefficient were evaluated by spectroscopic techniques. The cytotoxicity was assessed in vitro toward the human ovarian carcinoma cell line A2780, the human triple negative breast cancer cell line MDA-MB-231, and the human vascular smooth muscle cell line SMC. Some aminocarbyne complexes exhibited a potent cytotoxicity, with IC50 values in the low micromolar/nanomolar range, and a strong selectivity for the A2780 cells in comparison to the SMC cell line. Several experiments were carried out in order to give insight into the mode of action of selected compounds, including an assessment of catalytic NADH oxidation and ROS production and studies of binding with DNA and with a model protein.

A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η5-C5Me4R} Complexes with Variable R Groups

“…( a ) Octanol/water partition coefficients (Log P ow ). Partition coefficients (P ow ; IUPAC: K D partition constant [ 39 ]), defined as P ow = c org /c aq , where c org and c aq are molar concentrations of the selected compound in the organic and aqueous phase, respectively, were determined by the shake-flask method and UV-Vis measurements [ 40 ]. Deionized water and 1-octanol were vigorously stirred for 24 h, to enable saturation of both phases, then separated by centrifugation.…”

Spectroscopic Analysis of the Binding of Paraquat and Diquat Herbicides to Biosubstrates

“…Gel electrophoresis was used to determine the length of the fragments, being approximately 500 base pairs (100 bp DNA ladder is used as the reference). Stock solutions of ct-DNA were standardized spectrophotometrically (ε = 13,200 M −1 cm −1 at λ = 260 nm, I = 0.10 M, pH = 7.0—for the molar extinction coefficients see [ 45 ] and references therein); concentrations of ct-DNA are expressed in molarity of base pairs as C P (polynucleotide). The dried DNA oligonucleotide 5′-TAGGGTTAGGGTTAGGGTTAGGG-3′ (Tel23—hybrid, telomeric) was purchased from Metabion; its stock solution was prepared in aqueous buffer, and the molar concentration (in strands) was calculated according to the weight/content provided by the sample certificates.…”

Mono-, Di- and Tetra-iron Complexes with Selenium or Sulphur Functionalized Vinyliminium Ligands: Synthesis, Structural Characterization and Antiproliferative Activity

“…These limitations have fueled the research for the development of anticancer agents based on transition metals other than platinum [10][11][12][13][14][15][16][17][18][19][20][21], and in this respect mono-iron cyclopentadienyl compounds have been investigated, with substituted ferrocenes emerging as highly promising candidates [22][23][24]. Nevertheless, studies on poly-iron organometallic complexes still remain rare [25], and also iron-carbonyl compounds have been scarcely explored in the field so far [26][27][28].…”

“…Molecules 2020, 25, x FOR PEER REVIEW 2 of 21 [22][23][24]. Nevertheless, studies on poly-iron organometallic complexes still remain rare [25], and also iron-carbonyl compounds have been scarcely explored in the field so far [26][27][28]. Sulphur and selenium are found in a variety of organic molecules with therapeutic properties [29,30], and organo-selenium compounds have especially aroused interest for their anticancer potential, exerting their action alone or in combination with other drugs [31][32][33][34].…”