Antioxidative Activity of Ferrocenes Bearing 2,6-Di-Tert-Butylphenol Moieties

The antioxidative activity of ferrocenes bearing either 2,6-di-tert-butylphenol or phenyl groups has been compared using DPPH (1,1-diphenyl-2-picrylhydrazyl) test and in the study of the in vitro impact on lipid peroxidation in rat brain homogenate and on some characteristics of rat liver mitochondria. The results of DPPH test at 20°C show that the activity depends strongly upon the presence of phenolic group but is improved by the influence of ferrocenyl fragment. The activity of N-(3,5-di-tert-butyl-4-hydroxyphenyl)iminomethylferrocene (1), for instance, was 88.4%, which was higher than the activity of a known antioxidant 2,6-di-tert-butyl-4-methylphenol (BHT) (48.5%), whereas the activity of N-phenyl-iminomethylferrocene 2 was almost negligible −2.9%. The data obtained demonstrate that the compounds with 2,6-di-tert-butylphenol moiety are significantly more active than the corresponding phenyl analogues in the in vitro study of lipid peroxidation in rat brain homogenate. Ferrocene 1 performs a promising behavior as an antioxidant and inhibits the calcium-dependent swelling of mitochondria. These results allow us to propose the potential cytoprotective (neuroprotective) effect of ditopic compounds containing antioxidant 2,6-di-tert-butylphenol group and redox active ferrocene fragment

Thiouronium Salt Derivatives Based on Vicinal Diamines as Potential Neuroprotectors

Most of the medicinal products that are currently approved and used in clinical practice for neurodegenerative diseases, in particular Alzheimer’s disease, have a compensatory mechanism of action that enhances neurotransmitter signalling. It is an urgent need to develop new medicinal products combining cognitive-enhancing, neuroprotective, and disease-specific effects resulting from a multi-target mechanism of action including, in particular, prevention of glutamate-induced neuronal calcium uptake and stabilisation of microtubules.The aim of this study was to search for potentially neuroprotective and tauopathy-alleviating medicines amongst new thiouronium salt derivatives based on vicinal diamines.Materials and methods. The study investigated the ability of thiouronium salts to block glutamate-induced 45Ca2+ uptake by synaptosomes prepared from the brain of Wistar rats. The authors evaluated effects of these new compounds on polymerisation of a preparation of C57bl mouse brain tubulin and microtubule-associated proteins. The evaluation was carried out in the presence of guanosine triphosphate (GTP) and based on specific absorbance changes at 355 nm due to formation of microtubules. The authors analysed the structure of these microtubules, using negative staining followed by transmission electron microscopy. The IC50 determination and the statistical analysis were performed using standard software (Excel and PRISM 6.02).Results. The authors developed a screening algorithm for a number of new thiouronium salt derivatives based on vicinal diamines and studied biological activity of these derivatives by the effects on glutamate-induced calcium uptake by synaptosomes and on microtubule assembly processes. The authors identified compounds suppressing glutamate-induced calcium uptake by synaptosomes, i.e. compounds with neuroprotective potential. In addition, a number of new compounds were able to stimulate GTP-dependent microtubule assembly processes. The authors observed formation of microtubules with a normal structure in the presence of isopropyl-N’-[2-(benzoylamino)-1,2-diphenylethyl]-N-ethylimidothiocarbamate hydrobromide and considered the compound a promising scaffold for further optimisation.Conclusions. Chemical modification of thiouronium salts is a promising direction for developing effective neuroprotectors and microtubule stabilisers

Hybrid organotin compounds — modulators of apoptotic processes in the liver when administered once and repeatedly to WISTAR rats

Introduction. The aim of the study was to evaluate the effect of hybrid organotin compounds bis(3,5–di– tert–butyl–4–hydroxyphenylthiolate) dimethylol (Me3) and ((3,5–di–tert–butyl–4–hydroxyphenylthiolate) triphenylolol (Me5) on the level of markers of oxidative stress and apoptotic processes in the mitochondria during acute and subchronic intragastric administration to Wistar rats (females) in the maximum tolerated doseВведение. Цель исследования — оценка влияния гибридных оловоорганических соединений бис(3,5– ди–трет–бутил–4–гидроксифенилтиолат) диметилолова (Ме3) и ((3,5–ди–трет–бутил–4–гидроксифе- нилтиолат) трифенилолова (Ме5) на уровень маркеров окислительного стресса и апоптотических про- цессов в митохондрии при остром и субхроническом внутрижелудочном введении крысам линии Wistar (самки) в максимально переносимой доз

Study of acute oral toxicity of organotin compounds containing a 2,6-di-tert-butylphenol fragment

The aim of the study was to evaluate the safety of the use of organotin compounds containing a fragment of 2,6-di-tert-butylphenol as pharmaceutical substances when administered intragastrically to Wistar outbred rats (females)Цель исследования — оценка безопасности применения в качестве фармацевтических субстанций оловоорганических соединений, содержащих фрагмент 2,6-ди-трет-бутилфенола, при внутрижелудочном введении аутбредным крысам линии Wistar (самки)

Dichloro[<i>N</i>-[(η⁶-phenyl)methyl]-4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8tetrahydronaphthalen-2-yl)vinyl)benzamide](1,3,5-triaza-7-phosphatricyclo [3.3.1.1^3,7]decane-κP⁷)ruthenium

Bexarotene-tethered RuII(arene) compounds with 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (PTA) were prepared as an analog of RAPTA antitumor complexes in order to evaluate their in vitro antiproliferative activity against human cancer cell lines

Antiproliferative activity of ruthenium and osmium clusters with phosphine ligands

New ruthenium and osmium carbonyl clusters with 1,3,5-triaza-7-phosphatricyclo-[3.3.1.13.7]decane and 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane ligands were synthesized using Me3NO as an initiator. The data on antiproliferative activity of new compounds against ovarian carcinoma cell cultures A2780 (cisplatin-sensitive) and A2780cisR (cisplatin-resistant) are reported. The dependence of cytotoxicity on the number of phosphine ligands was demonstrated