Synthesis And Biological Activity Of Water-soluble Cationic Porphyrin Derivatives

G-quadruplex is a special secondary nucleic acid structure which consists ofG-rich DNA or RNA sequences. It is formed by π-π stacking interaction of differentplanar G-quartets which are made up of four guanine bases through hydrogen bondsconnecting both ends. And this structure mainly exists in fast divided cells such ascancer cells and tumor cells.Studies have shown that we can achieve anti-tumor effectby stabilizing G-quadruplex structure which can further suppress telomerase activity.Although small molecule ligands for example TMPyP4have been reported tostabilize G-quadruplex structure, they have an effect on double-stranded DNA as wellwhich indicates that they are nonspecific. Because G-quadruplexes often coexist orcompete with other configurations of DNA, it is necessary to separate them from thelatter ones. And designing ligands that can specifically recognize G-quadruplexesamong other types of DNA can solve the problem and can be very meaningful todesign anti-tumor and anti-cancer drugs. At the same time, whether G-rich sequencesand their complimentary C-rich sequences can form G-quadruplexes or form duplexhelix structures when they are together needs to be urgently investigated.Based on these considerations, the studies were as follows:1)5,10,15,20-tetra-{4-[3-(1-piperidinyl) propoxy] phenyl} porphyrin and thecationic porphyrin5,10,15,20-tetra-{4-[3-(1-methyl-1-piperidinyl) propoxy] phenyl}porphyrin were designed and synthesized. The structures were characterized by IR,MS and NMR etc..2) UV-Vis absorption, fluorescence and CD spectroscopic analysis showed thatTMPipPrOPP displayed distinctively different spectroscopic characters in thepresence of G-quadruplex DNAs comparing with that in the presence of duplex orsingle-stranded DNAs, which indicates that TMPipPrOPP can discriminateG-quadruplex from duplex and single-stranded DNA.TMPipPrOPP could bedeveloped as a highly specific G-quadruplex optical probe.3) The influence of a porphyrin derivative TMPipEOPP reported by our grouprecently on the G-quadruplex formations in the presence of long double-strandedDNAhad been studied by UV-vis and fluorescent spectra methods.4) Furthermore, the spectral properties and biological activities of the three new2-(4-hydroxyphenyl) imidazo [4,5-f]1,10-phenanthroline derivatives have beenstudied to introduce a new route for screening anticancer drugs targeting telomeric G-quadruplexes.