Synthesis and anti-cancer activity of aptamer-drug conjugates
Objective The conjugates of aptamer(58 nucleobases)and monomethyl auristatin E(MMAE)or exatecan(DX8951)were prepared to evaluate their inhibitory activity against human gastric cancer cells in vitro.Methods ApDCs(1a-1f,7a-7f)were synthesized by connecting MMAE or DX8951 to aptamer through linkers 4a-4d.The structures of synthesized compounds were confirmed through mass spectrometry and NMR analysis.Human gastric cancer cells were utilized as positive controls to assess the inhibitory activity of ApDCs(1a-1f,7a-7f)in vitro.Cell viability was quantified using CCK8 assay,and the cell proliferation inhibitory activity was determined by measuring the IC50 values for each ApDCs.Results 4 linkers and 12 ApDCs were synthesized.Cell proliferation inhibitory activity results demonstrated that all ApDCs(1a-1f,7a-7f)exhibited potent inhibitory activity.The IC50 values of 1a-1d,7a and 7c-7f were all below 100 nmol/L,which might have more safety than MMAE or DX8951 that has systemic toxicity.Conclusion ApDCs has obvious inhibitory effect on the proliferation of human gastric cancer cells,and has a potential application prospect in cancer treatment.
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