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: 2.47). 09/2008; 8(6):683-97.
Source: PubMed


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.

14 Reads
  • Source
    • "Recent advances in synthesis have afforded access to analogs of natural bacteriochlorophylls (Chen et al. 2004; Grin et al. 2008; Kozyrev et al. 2012), bacteriochlorins derived from porphyrins (e.g., Silva et al. 2005; Tomé et al. 2009; Singh et al. 2010; Pereira et al. 2011; Dabrowski et al. 2011; Samankumara et al. 2012; Aggarwal et al. 2014), and de novo synthesized bacteriochlorins (Minehan and Kishi 1999; Wang and Kishi 1999; Kim and Lindsey 2005; Krayer et al. 2010; for reviews see Galezowski and Gryko 2007; Brückner et al. 2012). The synthetic methodology we have developed to access bacteriochlorins is distinguished by (1) incorporation of geminal-dimethyl groups at the 8 and 18 positions to secure the chromophore from oxidative dehydrogenation leading to chlorins or porphyrins, (2) scalability, and (3) amenability to diverse reaction conditions. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Biohybrid light-harvesting architectures can be constructed that employ native-like bacterial photosynthetic antenna peptides as a scaffold to which synthetic chromophores are attached to augment overall spectral coverage. Synthetic bacteriochlorins are attractive to enhance capture of solar radiation in the photon-rich near-infrared spectral region. The effect of the polarity of the bacteriochlorin substituents on the antenna self-assembly process was explored by the preparation of a bacteriochlorin-peptide conjugate using a synthetic amphiphilic bacteriochlorin (B1) to complement prior studies using hydrophilic (B2, four carboxylic acids) or hydrophobic (B3) bacteriochlorins. The amphiphilic bioconjugatable bacteriochlorin B1 with a polar ammonium-terminated tail was synthesized by sequential Pd-mediated reactions of a 3,13-dibromo-5-methoxybacteriochlorin. Each bacteriochlorin bears a maleimido-terminated tether for attachment to a cysteine-containing analog of the Rhodobacter sphaeroides antenna β-peptide to give conjugates β-B1, β-B2, and β-B3. Given the hydrophobic nature of the β-peptide, the polarity of B1 and B2 facilitated purification of the respective conjugate compared to the hydrophobic B3. Bacteriochlorophyll a (BChl a) associates with each conjugate in aqueous micellar media to form a dyad containing two β-peptides, two covalently attached synthetic bacteriochlorins, and a datively bonded BChl-a pair, albeit to a limited extent for β-B2. The reversible assembly/disassembly of dyad (β-B2/BChl)2 was examined in aqueous detergent (octyl glucoside) solution by temperature variation (15-35 °C). The energy-transfer efficiency from the synthetic bacteriochlorin to the BChl-a dimer was found to be 0.85 for (β-B1/BChl)2, 0.40 for (β-B2/BChl)2, and 0.85 for (β-B3/BChl)2. Thus, in terms of handling, assembly and energy-transfer efficiency taken together, the amphiphilic design examined herein is more attractive than the prior hydrophilic or hydrophobic designs.
    Full-text · Article · Jul 2014 · Photosynthesis Research
  • 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.
    Full-text · Article · Aug 2013 · Journal of Porphyrins and Phthalocyanines
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Synthetic bacteriochlorins enable systematic tailoring of substituents about the bacteriochlorin chromophore and thereby provide insights concerning the native bacteriochlorophylls of bacterial photosynthesis. Nine free base bacteriochlorins (eight prepared previously and one prepared here) have been examined that bear diverse substituents at the 13- or 3,13-positions. The substituents include chalcone (3-phenylprop-2-en-1-onyl) derivatives with groups attached to the phenyl moiety, a "reverse chalcone" (3-phenyl-3-oxo-1-enyl), and extended chalcones (5-phenylpenta-2,4-dien-1-onyl, retinylidenonyl). The spectral and photophysical properties (τ(s) , Φ(f) , Φ(ic) , Φ(isc) , τ(T) , k(f) , k(ic) , k(isc) ) of the bacteriochlorins have been characterized. The bacteriochlorins absorb strongly in the 780-800 nm region and have fluorescence quantum yields (Φ(f) ) in the range 0.05-0.11 in toluene and dimethylsulfoxide. Light-induced electron promotions between orbitals with predominantly substituent or macrocycle character or both may give rise to some net macrocycle " substituent charge-transfer character in the lowest and higher singlet excited states as indicated by density functional theory (DFT) and time-dependent DFT calculations. Such calculations indicated significant participation of molecular orbitals beyond those (HOMO-1 to LUMO+1) in the Gouterman four-orbital model. Taken together, the studies provide insight into the fundamental properties of bacteriochlorins and illustrate designs for tuning the spectral and photophysical features of these NIR-absorbing tetrapyrrole chromophores. © 2013 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2013 The American Society of Photobiology.
    Full-text · Article · Jan 2013 · Photochemistry and Photobiology
Show more