Some cationic porphyrins: synthesis, stabilization of G-quadruplexes, and down-regulation of <i>c-myc</i> in Hep G2 cells

The stabilization of G-quadruplex DNA represents an attractive strategy for the design and development of novel antitumor drugs. In the present work, we have designed and synthesized nine cationic porphyrins, each with four side arms at their meso positions. The interactions of these porphyrins with both human telomeric DNA and NHE III 1 G-quadruplexes were measured by various DNA binding assays, including polymerase stop assay, circular dichroism (CD) and CD melting assay. We then proceeded to investigate their effects on the expression of c-myc oncogene in the Hep G2 cell line. The experimental results indicate that these porphyrins are capable of effectively inducing or stabilizing both human telomeric and NHE III 1 G-quadruplexes in the presence or absence of metal ions. Furthermore, we have discovered that porphyrins with a stronger stabilizing effect on c-myc G-quadruplexes lead to more pronounced down-regulation of the c-myc oncogene in the Hep G2 cell line.