| Hypoxia is an important characteristic of tumor microenvironment.The hypoxic cells in solid tumor result in tumors having strong resistance to radiotherapy,chemotherapy,et al.At the same time,hypoxic cells are the reason for local recurrence and malignant metastasis.So the detection and treating for hypoxic regions has practical significance,therefore,the study of hypoxia becomes a research hotspot.This article mainly includes the three parts as follow:1.Taken the poor hypoxia-selective cytotoxicity of 6H-indole[2,3-b]quinoxaline into consideration,“O” was introduced into the 11-position of 6H-indole[2,3-b]quinoxaline as N-oxides,and the 2-Nitroimidazole(remarkable hypoxia-activated property in tumor cells)was connected with carbon chain,then a series of 11-oxide-6H-indole[2,3-b]quinoxaline derivatives were synthesized and characterizated by IR,HRMS and NMR.And their cytotoxicity against Hela,MCF-7,A549 were investigated under normal and hypoxia conditions respectively via MTT test.Experimental data show that compounds exhibite excellent cytotoxicity and some of them display superior hypoxia-selectivity against the cell lines.2.P-nitrobenzene are the response groups of hypoxic and coumarin derivatives are fluorophore.Base on the two parts,a fluorescent probes to detect hypoxic was designed and synthesized in the manuscript.In tumor hypoxia cells,because of the action of the nitroreductase and triphosphopyridine nucleotide reduced tetrasodium salt(NADH),the probe can be reduced and the p-nitrobenzene is broken,then releasing the fluorescent molecule.And the structure of the synthetic compounds were verified by NMR,HRMS.The results show that the detection limit of the fluorescence method for nitroreductase is 48 ng/mL,and the response time of probe is 14 min,the probe did not show toxicity for Hela cells.The probe can be used to monitor the hypoxic status of tumor cells via the detection of endogenous nitroreductas. |
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