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Oxidative stress is related to the pathogenesis of many neurodegenerative disorders, including Parkinson's and Alzheimer's disease. The inability of the neuronal cells to maintain redox balance leads to free radicals accumulation, mitochondrial dysfunction, and neuronal injury.The neurons are highly sensitive to oxidative stress due to stronger dependence on oxidative phosphorylation, exposure to high concentrations of oxygen, and accumulation of metal ions during aging which increase the generation of reactive oxygen species. Other factors are the presence of easily oxidized polyunsaturated fatty acids and the relatively poor concentrations of antioxidants.A series of new benzimidazole hydrazones containing hydroxy and methoxy substituents were synthesized as analogues of Melatonin-a known antioxidant with neuroprotective action. The neurotoxicological potential of the compounds was assessed, and the derivatives demonstrating the most prominent effects were studied for neuroprotective properties in different in vitro models: H2O2-induced oxidative stress in neuroblastoma SH-SY5Y cells and 6-hydroxydopamine (6-OHDA) induced neurotoxicity in rat brain synaptosomes. As markers of oxidative damage, SH-SY5Y cell viability, synaptosomal viability, and intra-synaptosomal content of GSH were used.For further investigation of antioxidant properties, in vitro spectrophotometric model systems have been used. The antiradical activity against the stable free radicals ABTS and DPPH has been estimated, as well as the capability of the derivatives to decrease the level of molecular damage of biologically important molecules upon ferrous iron-induced oxidative molecular damage. The obtained data revealed that the tested compounds demonstrate a protective effect and capability to decrease the concentration of stable free radicals. Their potency depends of the used radical, oxidisable substrate, the type, and the position of the structural modification in the evaluated molecular structure.Different possible mechanisms, such as hydrogen atom transfer (HAT), single-electron transfer (SET-PT), and sequential proton loss electron transfer (SPLET), were studied by DFT methods.

The design of new drug candidates that combine anthelmintic and antioxidant actions in one molecule offers a beneficial approach in the treatment of the tissue damages, immune system dysfunction and oxidative stress caused by trichinellosis.

1H-benzimidazol-2-yl hydrazones with varying hydroxy and methoxy phenyl moieties were designed. Their effect on tubulin polymerization was evaluated in vitro on porcine tubulin. The compounds elongated the nucleation phase and slowed down the tubulin polymerization comparably to nocodazole. The possible binding modes of the hydrazones with tubulin were explored by molecular docking at the colchicine binding site. The anticancer activity was evaluated against human malignant cell lines MCF-7 and AR-230, as well as against normal fibroblast cells 3T3 and CCL-1. The compounds demonstrated a marked antineoplastic activity in low micromolar concentrations in both screened in vitro tumor models. The most active were the trimethoxy substituted derivative 1i and the positional isomers 1j and 1k, containing hydroxy and methoxy substituents: they showed IC50 similar to the reference podophyllotoxin in both tumor cell lines, accompanied with high selectivity towards the malignantly transformed cells. The compounds exerted moderate to high ability to scavenge peroxyl radicals and certain derivatives—1l containing metha-hydroxy and para-methoxy group, and 1b–e with di/trihydroxy phenyl moiety, revealed HORAC values high or comparable to those of well-known phenolic antioxidants. Thus the 1H-benisimidazol-2-yl hydrazones with hydroxy/methoxy phenyl fragments were recognized as new agents exhibiting promising combined antioxidant and antineoplastic action.

Fluorescent micellar carriers with controlled release of a novel anticancer drug were developed to enable intracellular imaging and cancer treatment simultaneously. The nanosized fluorescent micellar systems were embedded with a novel anticancer drug via the self-assembling behavior of well-defined block copolymers based on amphiphilic poly(acrylic acid)-block-poly(n-butyl acrylate) (PAA-b-PnBA) copolymer obtained by Atom Transfer Radical Polymerization (ATRP) and hydrophobic anticancer benzimidazole-hydrazone drug (BzH). Through this method, well-defined nanosized fluorescent micelles were obtained consisting of a hydrophilic PAA shell and a hydrophobic PnBA core embedded with the BzH drug due to the hydrophobic interactions, thus reaching very high encapsulation efficiency. The size, morphology, and fluorescent properties of blank and drug-loaded micelles were investigated using dynamic light scattering (DLS), transmission electron microscopy (TEM), and fluorescent spectroscopy, respectively. Additionally, after 72 h of incubation, drug-loaded micelles released 3.25 μM of BzH, which was spectrophotometrically determined. The BzH drug-loaded micelles were found to exhibit enhanced antiproliferative and cytotoxic effects on MDA-MB-231 cells, with long-lasting effects on microtubule organization, with apoptotic alterations and preferential localization in the perinuclear space of cancer cells. In contrast, the antitumor effect of BzH alone or incorporated in micelles on non-cancerous cells MCF-10A was relatively weak.

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