👤 da Silva PB

Due to their unique and versatile biochemical properties, ruthenium-based compounds have emerged as promising anticancer agents. Previous studies showed that three ruthenium(II) compounds: [Ru(pySH)(bipy)(dppb)]PF₆ (1), [Ru(HSpym)(bipy)(dppb)]PF₆ (2) and Ru[(SpymMe₂)(bipy)(dppb)]PF₆ (3) presented anticancer properties higher than doxorubicin and cisplatin and acted as human topoisomerase IB (Topo I) inhibitors. Here, we focused our studies on in vitro intestinal permeability and anticancer mechanisms of these three complexes. Caco-2 permeation studies showed that 1 did not permeate the monolayer of intestinal cells, suggesting a lack of absorption on oral administration, while 2 and 3 permeated the cells after 60 and 120 min, respectively. Complexes 2 and 3 fully inhibited Topo II relaxation activity at 125 µM. In previously studies, 3 was the most potent inhibitor of Topo I, here, we concluded that it is a dual topoisomerase inhibitor. Moreover, it presented selectivity to cancer cells when evaluated by clonogenic assay. Thus, 3 was selected to gene expression assay front MDA-MB-231 cells from triple-negative breast cancer (TNBC), which represents the highly aggressive subgroup of breast cancers with poor prognosis. The analyses revealed changes of 27 out of 84 sought target genes. PARP1 and PARP2 were 5.29 and 1.83 times down-regulated after treatment with 3, respectively. PARPs have been attractive antitumor drug targets, considering PARP inhibition could suppress DNA damage repair and sensitize tumor cells to DNA damage agents. Recent advances in DNA repair studies have shown that an approach that causes cell lethality using synthetic PARP-inhibiting drugs has produced promising results in TNBC. Show less

Tuberculosis is an ancient disease that is still present as a global public health problem. Our group has been investigating new molecules with anti-TB activity. In this context, inorganic chemistry has been a quite promising source of such molecules, with excellent results seen with ruthenium compounds. Nanostructured lipid systems may potentiate the action of drugs by reducing the required dosage and side effects and improving the antimicrobial effects. The aim of this study was to develop a nanostructured lipid system and then characterize and apply these encapsulated compounds (SCARs 1, 2 and 4) with the goal of improving their activity by decreasing the Minimum Inhibitory Concentration (MIC90) and reducing the cytotoxicity (IC50). The nanostructured system was composed of 10% phase oil (cholesterol), 10% surfactant (soy oleate, soy phosphatidylcholine and Eumulgin®) and 80% aqueous phase (phosphate buffer pH = 7.4). Good activity against Mycobacterium tuberculosis was maintained after the incorporation of the compounds into the nanostructured lipid system, while the cytotoxicity decreased dramatically, in some cases up to 20 times less toxic than the unencapsulated drug. Show less