Porphyrin-4`-bromoacetophenone Conjugates의 설계, 합성 및 DNA 절단 활성

Abstract

Photodynamic therapy, in which light activates a photosensitizing drug, is a type of cancer therapy based on the selective uptake and retention of photosensitizers such as porphyrins in tumor tissues. These compounds display cytotoxic effects when activated by light of particular wavelength. Porphyrin sensitizers have been a subject of intense research in the past decades because of their unique photophysical and pharmacokinetic properties. In order to increase the biological effectiveness and reduce toxicity of porphyrin as a sensitizer, their conjugation to various molecules, such as peptides, oligonucleotides, proteins, monoclonal antibodies, and small DNA cleaver have been investigated in recent years. With the aim to develop efficient photoinducible cytotoxic agent, porphyrin-4'-bromoacetophenone conjugates were designed as new photoinducible DNA cleavers. (Tri-p-tolyl)-(4-hydroxyphenyl) porphyrin and tetrakis( 4-hydroxyphenyl) porphyrin were synthesized and conjugated to 4'-bromoacetophenone, which can generate active carbon radicals upon irradiation and cleave DNA strand, through the appropriate linker. We describe the photolytic behavior of 4'-bromoacetophenone. The effect of the irradiation time of the compound on the photolysis was examined in order to optimize photoreaction condition. The photo cleaving activity of porphyrin-4'-bromoacetophenone conjugates were evaluated using the supercoiled plasmid pBR322 in the presence and absence of light.