Microwave-Assisted Synthesis of Imidazo[4,5-f][1,10]phenanthroline Derivatives as Apoptosis Inducers in Chemotherapy by Stabilizing Bcl-2 G-quadruplex DNA

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Li LiWen-Jie Zheng

Abstract

Herein, a series of imidazo[4,5-f][1,10] phenanthroline derivatives RPIP (PIP = imidazo [4,5-f][1,10] phenanthroline, R = NO₂,1; CF₃,2; Cl,3; OH,4) have been synthesized in yields of 82.3-94.7% at 100 °C under the irradiation of microwave. MTT assay has been utilized to evaluate the inhibitory activity (IC50) of these compounds against the growth of various tumor cells, and the results revealed that these compounds, especially1, exhibited excellent inhibitory activity against the growth of A549 cells with IC50of 15.03 μM. Moreover, it's also confirmed that1can penetrate into the membrane of tumor cells and distribute in mitochondria when observed under microscopy, resulting apoptosis of tumor cells. The further studies showed that1can bind tobcl-2G-quadruplex DNA, which demonstrated by the increase of melting point ofbcl-2G4 DNA in the presence of1, as well as electronic titration and emission spectra. In a word, this kind of compound may develop as a potential apoptosis inducer in cancer chemotherapy via binding and stabilizing to thebcl-2G-quadruplex DNA.

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Methods Mentioned

BETA
Fluorescence
flow cytometry
PCR

Software Mentioned

Origin7

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