No abstract

Previously, we reported the synthesis and structure-activity relationship (SAR) study of a series of novel 4,9-dioxo-4,9-dihydro-1H-naphthoij2,3-d]ij1,2,3]triazol-3-ium salts, which had very potent anti-proliferative activities (low μM to nM GI 50 ) against a broad range of cancer cells. These compounds, which can be viewed as cationic anthraquinone analogs (CAAs), are selective against cancer cells over bacteria or fungi as compared to the antibacterial CAAs that have also been reported by our group. Herein, we report a mode of action study of CAAs, which reveals that these compounds trigger apoptosis by generating extensive reactive oxygen species (ROS). The generation of extensive ROS causes oxidative stress, decrease in mitochondrial membrane potential, depletion of glutathione (GSH), and release of caspase-3, which ultimately kills cancer cells by programmed apoptosis. Furthermore, we have also shown that CAAs possess an 8-fold higher activity against the A549 cell line vs. the non-cancerous MRC-5 cell line.Med. Chem. Commun. This journal is

Low-temperature NMR studies with a4-C-methyl-4-O-benzoyl galactopyranosyl donor enable the observation and characterization of ab ridged bicyclic dioxacarbenium ion arising from participation by ad istal ester.V ariable-temperature NMR studies reveal this bridged ion to decompose at temperatures above %À30 8 8C. In the absence of the methyl group,t he formation of ab icyclic ion is not observed. It is concluded that participation by typical secondary distal esters in glycosylation reactions is disfavored in the ground state conformation of the ester from whichi ti ss tereoelectronically impossible.Methylation converts the secondary ester to aconformationally more labile tertiary ester,r emoves this barrier, and renders participation more favorable.N evertheless,t he minor changes in selectivity in model glycosylation reactions on going from the secondary to the tertiary esters at both low and room temperature argue against distal group participation being am ajor stereodirecting factor even for the tertiary system.

The background is a bright-field microscopic image ofCandida albicansthat is inhibited by amphiphilic kanamycinsFG08andK20.