Bacteriochlorophyll a, and its derivatives: chemistry and perspectives for cancer therapy.

Lomonosov Moscow Academy of Fine Chemical Technology, 86 Vernadsky Avenue, Moscow 119571, Russian Federation.
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) (Impact Factor: 2.94). 09/2008; 8(6):683-97.
Source: PubMed

ABSTRACT The review summarizes the chemistry of the third generation of photosensitizers, namely, the derivatives of natural bacteriochlorophyll a, for photodynamic treatment of cancer. The compounds of this class strongly absorb light at lambda=770-850 nm. This unique property opens new therapeutic opportunities due to deeper tissue penetration of light, thereby increasing the photodamage for tumor eradication. Analyzed are the modifications of bacteriochlorophyll a, that improve physico-chemical characteristics of compounds and enhance accumulation in tumors. Focusing on the delivery of photosensitizers to the tumor site and to specific intracellular compartments, we describe the conjugates of bacteriochlorophyll a, derivatives with carbohydrate and protein carriers. Boronated bacteriochlorins can be used in both photodynamic and boron neutron capture therapy.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bacteriochlorins are attractive candidates as photosensitizers for photodynamic therapy (PDT) due to their intense absorption in the near-infrared (NIR) region of the spectrum where light transmission through tissue is maximal. Many naturally occurring bacteriochlorins are inherently unstable due to adventitious atmospheric oxidation. A de novo synthesis affords bacteriochlorins that contain a geminal dimethyl group in each reduced pyrrole ring to increase stability against oxidation. Here, three new synthetic bacteriochlorins, each bearing a single side-chain containing one or two positive charges, were investigated for their in vitro PDT activity against HeLa human cancer cells. All bacteriochlorins were active at low nanomolar concentration when activated with NIR light; those bearing a single positive charge exhibited faster uptake and higher activity. The bacteriochlorins were localized in mitochondria, lysosomes and endoplasmic reticulum as shown by organelle specific fluorescent probes. Cell death was via apoptosis as shown by cell morphology and nuclear condensation. Taken together, the results show the importance of appropriate peripheral groups about a photosensitizer for effective PDT applications.
    Journal of Porphyrins and Phthalocyanines 01/2013; 17(1-2):73-85. DOI:10.1142/S108842461250126X · 1.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chlorophylls are a fundamental class of tetrapyrroles and function as the central reaction center, accessory and photoprotective pigments in photosynthesis. Their unique individual photochemical properties are a consequence of the tetrapyrrole macrocycle, the structural chemistry and coordination behavior of the phytochlorin system, and specific substituent pattern. They achieve their full potential in solar energy conversion by working in concert in highly complex, supramolecular structures such as the reaction centers and light-harvesting complexes of photobiology. The biochemical function of these structures depends on the controlled interplay of structural and functional principles of the apoprotein and pigment cofactors. Chlorophylls and bacteriochlorophylls are optically active molecules with several chiral centers, which are necessary for their natural biological function and the assembly of their supramolecular complexes. However, in many cases the exact role of chromophore stereochemistry in the biological context is unknown. This review gives an overview of chlorophyll research in terms of basic function, biosynthesis and their functional and structural role in photosynthesis. It highlights aspects of chirality and symmetry of chlorophylls to elicit further interest in their role in nature.
    Symmetry 09/2014; 6(3):781-843. DOI:10.3390/sym6030781 · 0.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Optimization of the chemical structure of antitumor photosensitizers (PSs) is aimed at increasing their affinity to a transport protein, albumin and irreversible light-induced tumor cell damage. Bacteriopurpurinimide derivatives are promising PSs thanks to their ability to absorb light in the near infrared spectral region. Using spectrophotometry, we show that two new bacteriopurpurinimide derivatives with different substituents at the N atoms of the imide exocycle and the pyrrole ring A are capable of forming non-covalent complexes with human serum albumin (HSA). The association constant (calculated with the Benesi-Hildebrand equation) for N-ethoxybacteriopurpurinimide ethyloxime (compound 1) is higher than that for the methyl ether of methoxybacteriopurpurinimide (compound 2) (1.18×10(5) M-1 vs. 1.26×10(4) M(-1), respectively). Molecular modeling provides details of the atomic interactions between 1 and 2 and amino acid residues in the FA1 binding site of HSA. The ethoxy group stabilizes the position of 1 within this site due to hydrophobic interaction with the protein. The higher affinity of 1 for HSA makes this compound more potent than 2 in photodynamic therapy for cultured human colon carcinoma cells. Photoactivation of 1 and 2 in cells induces rapid (within a few minutes of irradiation) necrosis. This mechanism of cell death may be efficient for eliminating tumors resistant to other therapies.
    01/2015; 7(1):109-16.