Parasitic infections, caused mainly by the species Trichinella spiralis (T. spiralis), are widespread around the world and lead to morbidity and mortality in the population. Meanwhile, some studies have showed that these parasites induce oxidative stress in the infected host. With the aim of developing a class of compounds combining anthelmintic with antioxidant properties, a series of new benzimidazolyl-2-hydrazones 5a-l, bearing hydroxyl- and methoxy-groups, were synthesized. The anthelmintic activity on encapsulated T. spiralis was studied in vitro thus indicating that all hydrazones were more active than the clinically used anthelmintic drugs albendazole and ivermectin. 5b and 5d killed the total parasitic larvae (100% effectiveness) after 24 hours incubation period at 37 °C in both concentrations (50 and 100 μg ml⁻¹). The antioxidant activity of the target compounds was elucidated in vitro against stable free radicals DPPH and ABTS as well as iron induced oxidative damage in model systems containing biologically relevant molecules lecithin and deoxyribose. The two 2,3- and 3,4-dihydroxy hydrazones 5b and 5d were the most effective radical scavengers in all studied systems. DFT calculations were applied to calculate the reaction enthalpies in polar and nonpolar medium and estimate the preferred mechanism of antioxidant activity. The relative radical scavenging ability of compounds 5a-l showed a good correlation to the experimentally observed trends. It was found that the studied compounds are capable to react with various free radicals – ˙OCH₃, ˙OOH and ˙OOCH₃, through several possible reaction pathways – HAT in nonpolar medium, SPLET in polar medium and RAF in both media.

In light of the known neuroprotective properties of indole compounds and the promising potential of hydrazone derivatives, two series of aldehyde-heterocyclic hybrids combining those pharmacophores were synthesized as new multifunctional neuroprotectors. The obtained derivatives of indole-3-propionic acid (IPA) and 5-methoxy-indole carboxylic acid (5MICA) had good safety profiles: Hemolytic effects < 5% (200 μM) and IC₅₀ > 150 µM were found in the majority of the SH-SY5Y and bEnd3 cell lines. The 2,3-dihydroxy, 2-hydroxy-4-methoxy, and syringaldehyde derivatives of 5MICA exhibited the strongest neuroprotection against H₂O₂-induced oxidative stress in SH-SY5Y cells and 6-OHDA-induced neurotoxicity in rat-brain synaptosomes. All the compounds suppressed the iron-induced lipid peroxidation. The hydroxyl derivatives were also the most active in terms of deoxyribose-degradation inhibition, whereas the 3,4-dihydroxy derivatives were able to decrease the superoxide-anion generation. Both series of compounds showed an increased inhibition of hMAO-B, with greater expression detected in the 5MICA hybrids. The in vitro BBB model with the bEnd3 cell line showed that some compounds increased the permeability of the endothelial monolayer while maintaining the tight junctions. The combined results demonstrated that the derivatives of IPA and 5MICA showed strong neuroprotective, antioxidant, MAO-B inhibitory activity and could be considered as prospective multifunctional compounds for the treatment of neurodegenerative disorders.

Objective: This study aimed to determine the capability of newly designed 3-methoxy derivatives of salicylaldehyde benzoylhydrazone to influence the oxidative stress processes and to test their in vitro cytotoxicity. Methods: We have used chemiluminescent and spectrophotometric model systems containing different types of reactive oxygen species (OH^●, OCl^─ and O₂^─●). The hydrazones effect on the viability of Hep-G2, HEK-293 and SH-SY5Y cell lines was determined via MTT assay. Results: The comparative analysis of the C₅₀ values of the chemiluminescent investigation demonstrated moderate activity against the hydroxyl radicals (C₅₀ > 50 μmol/L) and remarkable reactivity in the systems containing a superoxide radical and a hypochlorous anion (C₅₀ < 3.7 μmol/L). Further experiments in the spectrophotometric system of UV-induced OH^● generation and consequent 2′-deoxyribose oxidative damage excluded the possibility of quenching effect and proved the direct interaction of the studied compounds with that generated in the system reactive oxygen species (ROS). The encapsulation of the studied derivatives into chitosan-alginate particles led to the protection and stabilization of their antioxidant activity as revealed by a one-month study using the ABTS ^●+ method. The cytotoxic study revealed less pronounced effects against the non-malignant cell line (HEK-293) compared to Hep-G2 and SH-SY-5Y cells. Discussion: The incorporation of a hydroxyl group in the hydrazide part of a parent molecule which relates to better antioxidant effect in most of the studied systems is associated with higher IC₅₀ values in all cytotoxicity experiments and relates to the cytoprotective effect against N-methyl-D-aspartate-induced excitotoxicity in SH-SY5Y human neuronal cells.

In line with the well-established ethnobotanical use of Arum maculatum for the treatment of hemorrhoidal disease, we sought to determine the activities of 30% or 70% ethanol extracts of the plant tubers in an array of pharmacological and biochemical models of some crucial events implicated in the pathogenesis of this disorder, namely angiogenesis, collagenase activity remodeling, cyclooxygenase activity, IL-2 secretion and oxidative stress. The tested hydro-alcoholic extracts from A. maculatum tubers inhibited the proliferation of EA.hy926 vascular endothelial cells, but even at the highest administered concentrations no decrease in viability was observed. The extracts induced a concentration-dependent decrease in collagenase activity, whereby the effects were more pronounced at the lower concentration of ethanol in the extragent. Moreover the tested extracts induced concentration-dependent suppression of cyclooxygenase activity (COX-1 and 2), albeit at very high and presumably supraphysiological concentrations. The extracts augmented the PHA/PMA-induced secretion of IL-2 from Jurkat E.6 (human T-cells), which was more pronounced following exposure to the 30% ethanol-derived product. The 30% EtOH extract demonstrated anti-radical properties against both stable free radicals (ABTS and DPPH) and biologically relevant reactive oxygen species (ROS), which could be considered as important mediators of inflammation and signaling molecules. Our findings give us reason to conclude that the hydroalcoholic extracts of A. maculatum tubers possess anti-inflammatory, antiangiogenic and antioxidant effects which in concert could contribute to its efficacy for the management of hemorrhoidal disease.

Given the importance of molecular structure in pharmacological activity and interaction with biological receptors, we conducted a study on the 3,4-dihydroxybenzaldehyde hydrazone derivative of 5-methoxy-indole carboxylic acid (5MICA) and a newly synthesised analogue bearing a 2-methoxy-4-hydroxyphenyl ring using single-crystal X-ray diffraction. We studied the ability of the two compounds to scavenge hypochlorite ions using luminol-enhanced chemiluminescence and their potential to modulate oxidative damage induced by iron on the biologically significant molecules lecithin and deoxyribose in order to evaluate possible antioxidant and prooxidant effects. The X-ray study revealed highly conserved geometry and limited rotation and deformation freedom of the respective indole and phenyl fragments. Interestingly, a conformational difference between the two independent molecules in the asymmetric unit of 3b was found. The X-ray study revealed a combination of hydrogen bonding interactions, short contacts, and π–π stacking stabilizing the specific three-dimensional packing of the molecules of 3a and 3b in the crystal structures. The three-dimensional packing of the molecules of 3b produced a zigzag layering projected along the c-axis. Both compounds effectively decreased luminol-dependent chemiluminescence in model systems with KO₂-produced superoxide. They displayed opposite effects when applied in a xanthine/xanthine oxidase system. The hydrazones of 5MICA do not trigger a prooxidant effect or subsequent toxicity under conditions of iron-induced oxidative stress. The 3,4-dihydroxy-substituted derivative demonstrated excellent radical scavenging properties in all model systems, making it the lead compound for the development of compounds with combined neuroprotective and antioxidant properties.

The effect of La, Ce, Pr and Nd ions on four Ln(ligand)₃ complexes and at three DFT levels of calculation was analyzed. Four ligands were chosen, three of which were based on the 1,2,3-triazole ring. The DFT methods used were B3LYP, CAM-B3LYP and M06-2X. The relationships established were between the geometric parameters, atomic charges, HOMO-LUMO energies and other molecular properties. These comparisons and trends will facilitate the synthesis of new complexes by selecting the ligand and lanthanide ion best suited to the desired property of the complex. The experimental IR and Raman spectra of Ln(2b′)₃ complexes where Ln = La, Ce, Pr, Nd, Sm, Gd, Dy, Ho and Er ions have been recorded and compared to know the effect of the lanthanide ion on the complex. The hydration in these complexes was also analyzed. Additionally, the effect of the type of coordination center on the ability of an Ln(ligand)₃ complex to participate in electron exchange and hydrogen transfer was investigated using two in vitro model systems—DPPH and ABTS.