Studies On Design And Synthesis Of3,9-diazatetraasteranes As Anti-tumor Agents

Public health suffers more and more threat from cancer. With the development ofmolecular biological techniques and the in-depth knowledge of cancer pathogenesisby regulating molecular level from cell receptors and proliferation, molecular targeteddrug gradually become a research hotspot in the field of cancer treatment with itsfeatures such as strong specificity, pertinence and effectiveness. The3,9-diazatetraasterane was designed and synthesized as an anti-tumor agents by thevirtually screening. The article would provide theoretical and experimental basis tothe development of new molecular targeted drugs.Firstly, screening the anti-cancer molecular targets of3,9-diazatetraasteranes.The tetraethyl6,12-diphenyl-3,9-diazahexacyclo[6.4.0.02,7.04,11.05,10]dodecane-1,5,7,11-tetracarboxylate (Ia) was a sample as the initial structure to screening theanti-tumor molecular targets on Autodock4.0software platform by adopting thereverse molecular docking method. Fibroblast growth factor receptor-1(FGFR-1),fibroblast growth factor receptor-2(FGFR-2), janus kinase1(JAK1), janus kinase2(JAK2), glycogen synthase kinase3β (GSK-3β), focal adhesion kinases (FAK),farnesyltransferase (FTase), macrophage colony-stimulating factor receptor (cFAMS)and matrixmetallo proteinase-7(MMP-7) were chosen as the targets. The results showthat the FGFR-1, GSK-3β and MMP-7were indentified as three possible anti-tumortargets of3,9-diazatetraasteranes.Secondly, design and virtual screening of3,9-diazatetraasteranes as anti-tumoragents. The44of3,9-diazatetraasteranes with different substituent were docked withFGFR-1, GSK-3β and MMP-7using the method of molecular docking. The structuresof synthesis of target compounds were confirmed by the analyzing the dockingresults.In the end, research on the synthesizing3,9-diazatetraasteranes. Thephotostability of the4-aryl-N-aryl-1,4-dihydropyridines was studied using theoreticalcalculation and ultraviolet-visible spectroscopy. The4-aryl-N-aryl-1,4-dihydro-pyridines were chosen as the raw material and their [2+2] cycloaddition was studiedunder the irradiation of UV-light. The synthetic mechanism of3,9-diazatetraasteraneswas discussed by the electron paramagnetic resonance (EPR).