A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells.

BACKGROUND: Epithelial ovarian cancer has a poor prognosis, mostly due to its late diagnosis and the development of drug resistance after a first platinum-based regimen. The presence of a specific population of "cancer stem cells" could be responsible of the relapse of the tumor and the development of resistance to therapy. For this reason, it would be important to specifically target this subpopulation of tumor cells in order to increase the response to therapy. METHOD: We screened a chemical compound library assembled during the COST CM1106 action to search for compound classes active in targeting ovarian stem cells. We here report the results of the high-throughput screening assay in two ovarian cancer stem cells and the differentiated cells derived from them. RESULTS AND CONCLUSION: Interestingly, there were compounds active only on stem cells, only on differentiated cells, and compounds active on both cell populations. Even if these data need to be validated in ad hoc dose response cytotoxic experiments, the ongoing analysis of the compound structures will open up to mechanistic drug studies to select compounds able to improve the prognosis of ovarian cancer patients.

Multifunctional lipoic acid conjugates.

Several hundreds of studies published the last decade have reported that alpha-lipoic acid (LA) possess the potential to intervene in various therapeutically interesting pathways. However, it should be noted that LA reportedly exerts most of its effects at high micromolar concentrations; that amides of LA exhibit higher biological activity than the parent compound; and that molecular combinations (hybrids) obtained by coupling LA with an amino-substituted bioactive moiety, possess multifunctional activity. The design and synthesis of hybrid molecules encompassing two pharmacophores in one molecular scaffold is a well established approach to the synthesis of more potent drugs with dual activity. Using this approach, various research groups have recently designed and synthesized hybrid compounds with antioxidant activity hyphenated with a wide variety of other activities such as neuroprotective, cardioprotective, anti-inflammatory, antidiabetic and anticancer activity as well as enzyme inhibition. Moreover, LA represents an ideal chemical entity for the development of biologically interesting functionalized nanoparticles. Many recent publications describe the use of LA: i) as component of nanospheres and nanoprodrugs, ii) as a linker for the attachment of lipids, carbohydrates, proteins and oligonucleotides on gold nanoparticles to form Self Assembled Monolayers (SAMs) and iii) as surface ligand for cap exchange reactions to prepare water-soluble semiconducting nanocrystal Quantum Dots (QDs). This review is focused on the growing field of the design and synthesis of LA conjugates, for the development of novel molecules with a dual mode of action and the construction of nanosized antioxidants, Self Assembled Monolayers and Quantum Dots.

Novel potent inhibitors of lipid peroxidation with protective effects against reperfusion arrhythmias.

A series of new compounds that contain lipoic acid and trolox connected through spacers were synthesized and examined for their antioxidant activity and their protective effects against reperfusion arrhythmias in isolated heart preparations. All compounds tested are strong inhibitors of lipid peroxidation in rat liver microsomal membranes induced by ferrous ions and ascorbate. N-(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-carbonyl)-N'-(1,2-dithiolane-3-pentanoyl)-1,2-phenylenediamine (13) exhibits anti-lipid peroxidation activity at the nanomolar range. N-(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-carbonyl)-N'-(1,2-dithiolane-3-pentanoyl)ethylenediamine (10) and 13 totally suppressed reperfusion arrhythmias.