Synthesis and photophysical properties of amphiphilic halogenated bacteriochlorins: new opportunities for photodynamic therapy of cancer

Abstract

Photodynamic therapy (PDT) is a promising treatment for several types of cancers. It involves the synergetic effect of light, oxygen and an appropriate photosensitizer. Extensive studies on the synthetic modulation of the structure of tetrapyrrolic macrocycles allowed for the optimization of chemical and physical properties of such photosensitizers. The progress from porphyrins to chlorins and more recently to bacteriochlorins clearly shows the improvements achieved in PDT photosensitizers. This paper summarizes our recent contribution to the synthesis of stable amphiphilic halogenated meso-tetraarylbacteriochlorins. Their photophysics, in vitro cytotoxicity and phototoxicity are presented and their potential use as photosensitizer for PDT application is assessed.

New Halogenated Water‐Soluble Chlorin and Bacteriochlorin as Photostable PDT Sensitizers: Synthesis, Spectroscopy, Photophysics, and in vitro Photosensitizing Efficacy

“…[46,47] The reduction of TCPPSO 3 H to the corresponding chlorin (TCPCSO 3 H) and bacteriochlorin (TPCBSO 3 H) was carried out, based on our [48] recent modification of the classic Whitlock diimide reduction method. [49] Following standard reaction protocols, TCPPSO 3 H is dissolved in DMF in the presence of a non-nucleophilic organic compound (1,4-diazobicyclo[2.2.2]octane, DBO), followed by the addition of an eight or 40 molar excess of p-toluenesulfonylhydrazide, for chorin or bacteriochlorin synthesis, respectively, at 150 8C, for 12 h under inert atmosphere (Scheme 1).…”

Photocytotoxic activity of a nitrosyl phthalocyanine ruthenium complex — A system capable of producing nitric oxide and singlet oxygen

“…The photosensitizer itself is harmless, but a cascade of photochemical events takes place upon illumination in the presence of molecular oxygen, which results in the generation of highly cytotoxic singlet oxygen ( 1 O 2 ) and other reactive oxygen species (ROS) such as 1 O 2 , O 2 − •, OH•, and H 2 O 2 , responsible for oxidative biological damage and cell death [3,4]. A series of photosensitizers has been synthesized and their photochemical and photobiological properties have been described [5][6][7]. Haematoin porphyrin derivatives (HpD) such as Photofrin® comprise the first generation of photosensitizers approved for use in clinical therapy and have been utilized in the treatment of a variety of cancers in several countries over the last 20 years.…”

Tissue Uptake Study and Photodynamic Therapy of Melanoma‐Bearing Mice with a Nontoxic, Effective Chlorin

“…Direct comparison between the dark toxicities of photofrin and foscan reported in the literature and the dark toxicities of our halogenated and sulfonated photosensitizers determined here cannot be made because different cell lines and incubation times are involved; although, TCPPSO 3 H and TCPBSO 3 H have very similar dark toxicities towards various cell lines. [24,32] Nevertheless, a photofrin concentration of 15 mg mL À1 was reported to show statistically significant toxicity against S91 cells, [33] whereas this level of toxicity is only reached at a TCPCSO 3 H concentration of approximately 100 mm. Considering that the nominal molecular weight of photofrin is 600, [34] a crude estimate indicates that TCPCSO 3 H is about 25-times less toxic than photofrin.…”