An organocatalytic strategy for the synthesis of tetrasubstituted pyrrolidines with monoactivated azomethine ylides in high enantiomeric excess and excellent exo/endo selectivity is presented. The key to success is the intramolecular activation via hydrogen bonding through an o-hydroxy group, which allows the dipolar cycloaddition to take place in the presence of azomethine ylides bearing only one activating group. The intramolecular hydrogen bond in the azomethine ylide and the intermolecular hydrogen bond with the catalyst have been demonstrated by DFT calculations and mechanistic proofs to be crucial for the reaction to proceed.

A group of styrylquinolines were synthesized and tested for their anti-proliferative activity. Anti-proliferative activity was evaluated against the human colon carcinoma cell lines that had a normal expression of the p53 protein (HCT116 p53^+/+) and mutants with a disabled TP53 gene (HCT116 p53^-/-) and against the GM 07492 normal human fibroblast cell line. A SAR study revealed the importance of Cl and OH as substituents in the styryl moiety. Several of the compounds that were tested were found to have a marked anti-proliferative activity that was similar to or better than doxorubicin and were more active against the p53 null than the wild type cells. The cellular localization tests and caspase activity assays suggest a mechanism of action through the mitochondrial pathway of apoptosis in a p53-independent manner. The activity of the styrylquinoline compounds may be associated with their DNA intercalating ability.

Styrylquinolines are a novel group of quinoline drugs that are known to have p53-independent antiproliferative activity and antiviral properties. This study evaluated the antifungal activity of these drugs more deeply, particularly their activity modulation towards Cdr1p, the main multidrug transporter of Candida albicans. Styrylquinolines were found to have antifungal activity and to work synergistically with fluconazole. Additionally, they decreased the extracellular concentration of rhodamine 6G in ABC-transporter-expressing cells. The cellular localization of GFP-tagged Cdr1p was assessed by epifluorescent microscopy. Styrylquinolines induce expression of Cdr1p, as confirmed by Western blotting. Three of four drugs tested caused the partial delocalization of transport protein to the cytoplasm. These results show the first evidence that styrylquinolines decrease the activity of ABC multidrug transporters in C. albicans.