BackgroundRecently, various metallocenes were synthesized and analyzed by biological activity point of view (such as antiproliferative properties): ruthenocenes, cobaltoceniums, titanocenes, zirconocenes, vanadocenes, niobocenes, molibdocenes etc. Two main disadvantages of metallocenes are the poor hydrosolubility and the hydrolytic instability. These problems could be resolved in two ways: synthetically modifying the structure or finding new formulations with enhanced properties. The aqueous solubility of metallocenes with cytostatic activities could be enhanced by molecular encapsulation in cyclodextrins, as well as the hydrolytic instability of these compounds could be reduced.ResultsThis study presents a theoretical approach on the nanoencapsulation of a series of titanocenes with cytotoxic activity in α-, β-, and γ-cyclodextrin. The HyperChem 5.11 package was used for building and molecular modelling of titanocene and cyclodextrin structures, as well as for titanocene/cyclodextrin complex optimization. For titanocene/cyclodextrin complex optimization experiments, the titanocene and cyclodextrin structures in minimal energy conformations were set up at various distances and positions between molecules (molecular mechanics functionality, MM+). The best interaction between titanocene structures and cyclodextrins was obtained in the case of β- and γ-cyclodextrin, having the hydrophobic moieties oriented to the secondary face of cyclodextrin. The hydrophobicity of titanocenes (logP) correlate with the titanocene-cyclodextrin interaction parameters, especially with the titanocene-cyclodextrin interaction energy; the compatible geometry and the interaction energy denote that the titanocene/β- and γ-cyclodextrin complex can be achieved. Valuable quantitative structure-activity relationships (QSARs) were also obtained in the titanocene class by using the same logP as the main parameter for the in vitro cytotoxic activity against HeLa, K562, and Fem-x cell lines.ConclusionsAccording to our theoretical study, the titanocene/cyclodextrin inclusion compounds can be obtained (high interaction energy; the encapsulation is energetically favourable). Further, the most hydrophobic compounds are better encapsulated in β- and γ-cyclodextrin molecules and are more stable (from energetically point of view) in comparison with α-cyclodextrin case. This study suggests that the titanocene / β- and γ-cyclodextrin complexes (or synthetically modified cyclodextrins with higher water solubility) could be experimentally synthesized and could have enhanced cytotoxic activity and even lower toxicity.

No abstract

Issues concerning chemical compounds studied in the framework of metallomics are of interest both for the domain of biochemistry dealing with the metabolization of nutrients and for xenobiochemistry -a different domain of biochemistry dealing with the biodegradation of xenobiotics. In this context, in vivo and in vitro data are reviewed here on inorganic and organo-metallic compounds of gallium (Ga), ranging from cellular and molecular biology to biochemistry and pathobiochemistry and on to pharmacology and its relations to homeostasis and nutrient degradation.Keywords: gallium compounds -biochemistry; xenobiochemistry; biomedical effects; in vivo; in vitro МЕТАЛОМИКА НА ГАЛИУМОВИ СОЕДИНЕНИЈА: БИОХЕМИСКИ И КСЕНОБИОХЕМИСКИ АСПЕКТИ Проблемите поврзани со хемиските соединенија од областа на металомиката се од интерес не само за биохемијата -домен што се занимава со метаболизмот на хранливите состојки, туку и за ксенобиохемијата -дел од биохемијата што се занимава со биодеградацијата на ксено-биотиците. Во овој труд е направен преглед на податоците in vitro и in vivo за неоргански и органски соединенија на галиум, од аспект на клеточна и молекуларна биологија до биохемија и патобиохемија и фармакологија во однос на хомеостазата и разложувањето на хранливите состојки.Клучни зборови: биохемија; ксенобиохимија; биомедицинско дејство; соединенија на галиум in vivo; in vitro

Interactions between metal ions and biological systems have many implications. Based on these facts, several platinum compounds have been obtained and evaluated as chemotherapeutical agents. It is generally believed that the anticancerous effects of cis-platinum are based on interactions with DNA. Our study is trying to reveal the interrelations between concentration of some metallic ions from hepatic tissue and different doses of cis-platinum (cDDP). The cytotoxic activity of cis-platinum can be correlate with the levels of platinum that bounds to DNA. For the experimental part, we used adults animals from Wistar rats strain divided in four experimental groups and one control group. Wistar rats from the experimental groups were injected intraperitoneally (i.p.) with cis-platinum (the drug called Sin-Platinum) in study days 3 and 8. The animals from control group were injected with saline solution (placebo), also in study days 3 and 8. The results showed that the concentration of metal ions in liver is modified proportionally with administrated doses.

Аннотация. В статье представлены данные о статусе некоторых важных биоэлементов, которые действуют как кофакторы для различных ферментов у крыс с индуцированным окислительным стрессом при введении алюминия и цисплатина. Исследование было проведено на тридцати шести молодых крысах-альбиносах Вистар (3-месячного возраста), разделённых методом случайного выбора на четыре группы следующим образом: С-контроль, 1 мл физиологического раствора (ФР); E1-введение AlCl3 100 мг/кг массы тела; Е2-введение 10 мг/кг массы тела цисплатина; E3-введение 100 мг/кг массы тела AlCl3 и 10 мг/кг массы тела цисплатина. Все введения осуществлялись внутрибрюшинным путём (внутрибрюшинно) один раз в неделю в течение четырёхнедельного периода. Были измерены окислительный стресс, ферменты CAT (каталаза), SOD (супероксиддисмутаза), глутатионпероксидаза (GPx), глутатионредуктаза (GSH-r) и уровни в крови железа, марганца, магния, меди, цинка и селена. Во всех экспериментальных группах наблюдалось значительное снижение CAT, значительное увеличение GPx и GSH-r, незначительное увеличение SOD, незначительные колебания марганца и магния, значительное снижение цинка и меди и незначительное снижение селена. Мы можем заключить, что алюминий и цисплатин могут нарушать нормальное состояние основных биоэлементов через индуцированный окислительный стресс.