Total synthesis of compounds 2-Aziridin-1-yl-3-[(2 - (2 - [(3- aziridin-1-yl-1 ,4-dihydronaphthalen-2-yl) thio] ethoxy) ethyl) thio] naphthoquinone ( AZ-1) causes of oral cancer cell
death mechanism
Abstract
Has pointed out that aziridinylbezoquinone compounds with anticancer activity, of which the aziridine structure can alkylate DNA, inhibiting DNA replication. In this thesis, the full synthetic drugs used in AZ-1 in the structure with two aziridine rings, and is located in two with - (CH2) 2-O-(CH2) 2 - naphthoquinone on bridging the connection. AZ-1 对 CT-5 'cells LD50 is 0.8 μ M, with the AZ-1 dose and reaction time increased, while cytotoxicity
increased. This paper has entered clinical trials with the drug AZQ comparison, AZQ is aziridinylbenzoquinone compounds, with two aziridine rings. The experimental results show that AZQ on the CT-5 'cells of the LD50 is 50 μ M. AZ-1 was found and a similar structure, but no aziridine ring of the BQ, the LD50 is 8 μ M. It was found that when both joined the U0126 and the AZ-1, may reduce the AZ-1 对 CT-5 'cytotoxicity. Hoechst staining was found in the AZ-1
concentration of 2 μ M, there will be the appearance of apoptotic bodies. The AZ-1 concentration 0.125 μ M ~ 1 μ M, the cells will remain at the G2 / M phase, when AZ-1 concentration of 2 μ M, then there is apoptosis phenomenon. p53 protein expression with the AZ-1 concentration would be increased, at a concentration of 2 μ M, the increase 69%, but p21 protein expression was not changed.
G2 / M phase-related proteins Cyclin B is about 50% increase in performance, but Cdc2 protein expression and not with the AZ-1 concentration increased significantly change. Speculated that AZ-1 causes oral cancer cell CT-5 'causes of death and p53 protein
related to the concentration of 1 μ M in the following caused the cells to stop in G2 / M phase, and when the concentration of 2 μ M, then can induce programmed cell death.
English Abstract
