Use solid-supported benzannulation reaction and the subsequent oxidative cleavage

Of note, are the anti-malarial naphthoquinones, particularly hydroxyl-1, 4-naphthoquinone, which is used in combination with proguanil for the prevention and treatment of malaria. In an effort to create 1, 4-naphthoquinone libraries a novel organic synthesis regime was developed using microwaveassisted solid-phase Dotz benzannulation H3B-6527 reactions. This was the first report to use solid-supported benzannulation reaction and the subsequent oxidative cleavage process to Aceclofenac generate derivatives of this class of quinones. Here, twelve different 2, 3-disubstituted-1, 4-naphthoquinones synthesized using this regime were screened for biological activity against the murine fibroblast cell line, L929. The L929 cell line was chosen to serve as the adherent cell assay model due to its ease of use and its frequent use in toxicity assays for various agents. The data demonstrates that the majority of the naphthoquinones studied were cytotoxic and promoted the induction of ROS formation. To assess the effect of our small library of compounds on the morphology of the cells, the fibroblasts were cultured in 4chamber well slides in the presence of each compound at the IC50. Following a incubation, the slides were assessed by light microscopy. Untreated cells presented with two general morphologies: adherent-fibrous and semi-adherent rounded, which is typical of this cell line in different phases of the cell cycle. Similar morphologies were seen for cells treated with the vehicle control. In contrast, hydrogen peroxide treated cells were rounded, granular, and vesiculated, which is typical of dying cells. At a single concentration, the compounds either had no effect on the cells, as represented by compound 9, or were detrimental to cell survival, as represented by compounds 2 and 5, further demonstrating that members of our small compound library were cytotoxic. We next assessed possible mechanisms the cytotoxic compounds could be utilizing to inhibit cell survival. We first assessed the loss of plasma membrane phosphatidylserine asymmetry.