Oxonitrogenated Derivatives of Eremophilans and Eudesmans: Antiproliferative and Anti-Trypanosoma cruzi Activity

Cancer is one of the most important causes of death worldwide. Solid tumors represent the vast majority of cancers (>90%), and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpenes are a group of natural compounds that have shown a wide range of biological activities, including cytotoxic and antiparasitic activity, among others. The antiproliferative activity of natural sesquiterpenes, tessaric acid, ilicic acid, and ilicic alcohol and their semisynthetic derivatives against HeLa, T-47D, WiDr, A549, HBL-100, and SW1573 cell lines were evaluated. The effect of the compounds on Trypanosoma cruzi epimastigotes was also assessed. The selectivity index was calculated using murine splenocytes. Derivatives 13 and 15 were the most antiproliferative compounds, with GI₅₀ values ranging between 5.3 (±0.32) and 14 (±0.90) μM, in all cell lines tested. The presence of 1,2,3-triazole groups in derivatives 15–19 led to improvements in activity compared to those corresponding to the starting natural product (3), with GI₅₀ values ranging between 12 (±1.5) and 17 (±1.1) μM and 16 being the most active compound. In relation to the anti-T. cruzi activity, derivatives 7 and 16 obtained from tessaric acid and ilicic acid were among the most active and selective compounds with IC₅₀ values of 9.3 and 8.8 µM (SI = 8.0 and 9.4), respectively.     

Novel Iron Oxide Nanoparticles Induce Ferroptosis in a Panel of Cancer Cell Lines

The use of nanomaterials rationally engineered to treat cancer is a burgeoning field that has reported great medical achievements. Iron-based polymeric nano-formulations with precisely tuned physicochemical properties are an expanding and versatile therapeutic strategy for tumor treatment. Recently, a peculiar type of regulated necrosis named ferroptosis has gained increased attention as a target for cancer therapy. Here, we show for the first time that novel iron oxide nanoparticles coated with gallic acid and polyacrylic acid (IONP–GA/PAA) possess intrinsic cytotoxic activity on various cancer cell lines. Indeed, IONP–GA/PAA treatment efficiently induces ferroptosis in glioblastoma, neuroblastoma, and fibrosarcoma cells. IONP–GA/PAA-induced ferroptosis was blocked by the canonical ferroptosis inhibitors, including deferoxamine and ciclopirox olamine (iron chelators), and ferrostatin-1, the lipophilic radical trap. These ferroptosis inhibitors also prevented the lipid hydroperoxide generation promoted by the nanoparticles. Altogether, we report on novel ferroptosis-inducing iron encapsulated nanoparticles with potent anti-cancer properties, which has promising potential for further in vivo validation.     

An Investigation of Complexation of Cadmium(II) with Arginine

Among amino acids, arginine is important in human physiology because it plays an important role in cardiovascular and depression problems. In this paper the behavior of arginine as a ligand toward cadmium(II) [Cd(II)] in two different ionic media: 1.00 mol·dm^?3 NaCl and NaClO₄, is studied. Knowledge of the species formed between Cd(II) and arginine in a wide concentration range is useful also in biology. This system was investigated using two different methods in two ranges of hydrogen ion concentration. In acidic solutions, electromotive force measurements are performed using glass and Cd amalgam electrodes. In basic solutions, polarography was used and the shift of the half wave potential was measured as a function of the ligand concentration. The experimental data obtained in NaCl solutions are explained by assuming the formation of the species [CdL], [CdHL], [CdL₂], [CdHL₂] and [CdH₂L₂]. The data obtained in NaClO₄ solutions are explained by assuming the formation of the species [CdL], [CdHL], and [CdH₂L₂]. In both cases the stability constants are reported.     

THE EFFECT OF ALCOHOLS WITH DIFFERENT STRUCTURES ON THE FORMATION OF WARM O/W MICROEMULSIONS

The influence of twenty five different alcohols on the formation of warm oil-in-water (O/W) microemulsions was investigated. Selected concentrations of each alcohol were added to fixed amounts of stearic acid, Tween 20 and water at 65 ° C. Fifteen alcohols formed microemulsions, at least at one of the concentrations. A pattern recognition study was performed to elucidate the activities of the alcohols by Principal Component Analysis (PCA). Linear Discriminant Analysis (LDA) was used to classify them. Two classification functions, obtained for alcohols forming / not forming microemulsions, suggest that the formation of warm O/W microemulsion is linked to the nature and the dimension/lipophilicity of the alcohol.     

An Experimental Study of a Flux Modulated Solid State Metathesis Reaction

A solid state metathesis (SSM) reaction was investigated with respect to the formation of rare‐earth carbodiimides, the role of the co‐produced salt (LiCl), and the eutectic flux medium (LiCl/KCl). A SSM reaction is characterized by an exothermic reaction in which a salt (often LiCl) is coproduced. When the salt melts, it can serve as a useful medium for the crystallization of a desired product. An improved crystal growth can be observed by using an eutectic flux. However, the composition of an eutectic LiCl/KCl flux is altered when LiCl is produced during the reaction. The thermal effects concerning the endothermic melting of the flux and the exothermic ingnition of the SSM reaction may compensate each other, which is not necessarily a drawback for the reaction to proceed.     

Magnetic Anisotropy of Dichlorobis(η5‐cyclopentadienyl) Complexes of Vanadium,Niobium, and Tantalum

Abstract. The magnetic behavior of the mononuclear nd¹ systems MCp₂Cl₂ (M = V⁴⁺[3d¹], Nb⁴⁺[4d¹], Ta⁴⁺[5d¹], space group P2₁/c, pseudosymmetry of the molecules C_2v) deviates from pure single ion spin magnetism on account of ligand field effect (H_lf), spin‐orbit coupling (H_so), and intermolecular spin‐spin exchange interactions (H_ex). For both VCp₂Cl₂ and NbCp₂Cl₂ excellent adaptations to the measured susceptibility data were obtained (2 K ≤ T ≤ 300 K) on the basis of spectroscopic data (lf, so) and cooperative metal–metal interactions (ex) of antiferromagnetic nature [molecular field model (mf)]. For TaCp₂Cl₂ experimental term structure data are not available. Therefore, Jørgensen's spectroscopical series (g‐factor of the central ion) was applied to extrapolate the data set for TaCp₂Cl₂. H_lf, H_so, and H_ex (antiferromagnetic) increase in the order 3d¹ → 4d¹ → 5d¹ leading, with rising atomic number of the metals, to a distinct enhancement of the magnetic anisotropy. At 4 K the μ_eff components μ_eff,y (oriented perpendicular to the cg–M–cg plane; “cg” = center of gravity of the Cp ring), μ_eff,z (oriented along the twofold pseudoaxis), and μ_eff,x are 1.73, 1.69, 1.68 (V), 1.73, 1.62, 1.59 (Nb), and 1.71, 1.59, 1.49 (Ta). While μ_eff,y is independent of T, both μ_eff,z and μ_eff,x decrease with decreasing T.