15664-29-6Relevant academic research and scientific papers
ELECTROPHILIC SUBSTITUTION AT THE δ-METHINE BRIDGE OF PHEOPHORBIDE a AND a'
Hynninen, Paavo H.,Loetjoenen, Simo
, p. 1845 - 1846 (1981)
A chloro-substituted derivative was prepared from chlorophyll a'.The derivative was shown to be δ-chloro-methyl pheophorbide a by UV/VIS, MS and 1H NMR.
Anti-tumor evaluation of a novel methoxyphenyl substituted chlorin photosensitizer for photodynamic therapy
Cao, Lei,Dong, Yi,Li, Guangzhe,Li, Yueqing,Wang, Liu,Zhao, Weijie
, (2020)
Photodynamic therapy (PDT) is a non-invasive and innovative therapeutic approach which has been increasingly applied in clinical cancer therapy. As the central element of PDT, the development of novel photosensitizers (PSs) with longer absorption wavelength, proper lipophilic/hydrophilic profiles, target tissue selectivity, and higher photo?/lowest dark-cytotoxicity is a challenging task. Previously, we designed and synthesized a series of novel long-wavelength chlorin e6 (Ce6)-based PSs via introducing aromatic groups to the vinyl of Ce6 skeleton. The new formed compounds with π-extension system exhibited improved photodynamic effects and spectral characteristics. Among these π-conjugated chlorin PSs, (E)-32-(4-methoxyphenyl)-chlorin e6, named A15, was expected to be a potent antitumor candidate as a PDT agent due to its good photobiological properties. Herein, in this work, we evaluated the effectiveness of A15 in cancer PDT. In vitro, a novel rare earth probe, ATTA-Eu3+ was applied to detect the singlet oxygen (1O2) production of A15 in solution and human hepatoma HepG2 cells, respectively. Moreover, A15 exhibited strong phototoxicity and weak dark cytotoxity to HepG2 cells. In H22 tumor bearing mice, A15 showed excellent tumor accumulation ability via i.v. administration and induced tumor regression, followed by laser treatment. These results indicated that A15 is a potential novel π–extension chlorin-type PS for PDT applications.
Effect of dietary chlorophyll derivatives on mutagenesis and tumor cell growth
Chernomorsky, Simon,Segelman, Alvin,Poretz, Ronald D.
, p. 313 - 322 (1999)
Much attention in recent years has been given to the antigenotoxicity of chlorophyll. Chlorophyll, however, is known to be converted into pheophytin, pyropheophytin, and pheophorbide in processed vegetable food and following ingestion by humans. Studies were conducted on the antimutagenic and tumoricidal potencies of these compounds. All the chlorophyll derivatives tested exhibit identical antimutagenic effect towards 3-methylcholanthrene (3-MC), suggesting that the porphyrin nucleus may complex directly with the mutagen. It does not exclude, however, another mechanism of activity involving inactivation the enzymatic transformation of 3-MC. In contrast, the action of N'-nitro-N'-nitrosoguanidine (MNNG) depends upon structural differences between the chlorophyll derivatives. It is significantly lower when the phytol-containing pheophytin and pyropheophytin are tested as to that of the phytol-lacking pheophorbide. The higher concentrations of the chlorophyll derivatives were required to reduce the mutagenicity of MNNG than needed for 3-MC. The cytotoxicity of chlorophyll derivatives against tumor cells also was evaluated. The cellular uptake and inhibition of myeloma cell multiplicity were found to be greater for pheophorbide than for pheophytin. Calculated on the amount of cell associated chlorophyll derivative, however, pheophytin was more cytostatic/cytotoxic than pheophorbide. The results presented in this report indicate that food sources that yield chlorophyll derivatives may play a significant role in cancer prevention.
Synthesis of potential antitumor agents, dimeric and trimeric chlorins, from methylpheophorbide a
Belykh,Mal'Shakova,Yudina,Zavadskaya,Khudyaev,Kuchin
, p. 719 - 728 (2011)
A series of dimeric and trimeric chlorins were synthesized from methylpheophorbide a. They are potential photosensitizers for photodynamic therapy in oncology. The macrocycles were conjugated due to the formation of ester and amide bonds. The carboxy groups were activated and catalytic transesterification was carried out to form the ester bond. The amide bond was formed using carboxy group activation; in several cases, amidation of the ester group in position 13(2) of the exocycle of methylpheophorbide α was carried out, which does not require activation.
Design, synthesis and biological evaluation of novel 31-hexyloxy chlorin e6-based 152- or 131-amino acid derivatives as potent photosensitizers for photodynamic therapy
Zhang, Xing-Jie,Han, Gui-Yan,Guo, Chang-Yong,Ma, Zhi-Qiang,Lin, Mei-Yu,Wang, Yuan,Miao, Zhen-Yuan,Zhang, Wan-Nian,Sheng, Chun-Quan,Yao, Jian-Zhong
, (2020)
This study aimed to improve the biological effectiveness and pharmacokinetic properties of chlorin e6, a second-generation photosensitizer (PS), for tumor photodynamic therapy (PDT). Herein, the novel 31-hexyloxy chlorin e6-based 152- or 131-amino acid derivatives 3a, 3b, 3c and 8 were synthesized and their photophysical properties and in vitro bioactivities such as phototoxicity against A549, HeLa and melanoma B16–F10 cells, reactive oxygen species (ROS) production and subcellular localization were evaluated. In addition, preferred target compounds were also investigated for their in vivo pharmacokinetic in SD rats and in vivo antitumor efficacies in C57BL/6 mice bearing melanoma B16–F10 cells. Apparently, simultaneous introduction of amino acid residue and n-hexyloxy chain in chlorin e6 made a significant improvement in photophysical properties, ROS production, in vitro and in vivo PDT efficacy. Encouragingly, all target compounds showed higher in vitro phototoxicity than Talaporfin, and that 3c (152-Lys) exhibited strongest phototoxicity and highest dark toxicity/phototoxicity ratio, followed by 8 (131-Asp), 3a (152-Asp) and 3b (152-Glu). Moreover, in vivo PDT antitumor efficacy of 3a, 3c and 8 was all better than that of Talaporfin, and that both 3c and 8 had stronger PDT antitumor efficiency than 3a. The overall results suggested that these novel 31-hexyloxy chlorin e6-based 152- or 131-amino acid derivatives, especially 3c and 8, might be potential antitumor candidate drugs for clinical treatment of melanoma by PDT.
Synthesis and biological evaluation of new water-soluble photoactive chlorin conjugate for targeted delivery
Otvagin, Vasilii F.,Nyuchev, Alexander V.,Kuzmina, Natalia S.,Grishin, Ivan D.,Gavryushin, Andrei E.,Romanenko, Yuliya V.,Koifman, Oscar I.,Belykh, Dmitrii V.,Peskova, Nina N.,Shilyagina, Natalia Yu,Balalaeva, Irina V.,Fedorov, Alexey Yu.
, p. 740 - 750 (2018)
A new water-soluble conjugate, consisting of a chlorin-based photosensitizing part, and a 4-arylaminoquinazoline moiety with high potential affinity to an epidermal growth factor receptors (EGFR) and vascular endothelial growth factor receptors (VEGFR), suitable for photodynamic therapy (PDT), was synthesized starting from methylpheophorbide-a in seven steps. An increased accumulation of this compound in A431 cells with high level of EGFR expression, in comparison with CHO and HeLa cells with low EGFR expression was observed. The prepared conjugate exhibits dark and photoinduced cytotoxicity at micromolar concentrations with IC50dark/IC50light ratio of 11–18. In tumor-bearing mice, the conjugate preferentially accumulates in the tumor tissue.
Synthesis of chlorins with a distal vinyl group
Mal'Shakova,Belykh,Kuchin
, p. 197 - 200 (2007)
A series of chlorins containing a vinyl group on the periphery of the chlorin ring that was attached by linkers of various length, potential monomers for synthesis of polymers containing chlorin via copolymerization, was synthesized from methylpheophorbide a.
Synthesis of pheophorbide-a conjugates with anticancer drugs as potential cancer diagnostic and therapeutic agents
You, Hyun,Yoon, Hyo-Eun,Yoon, Jung-Hoon,Ko, Hyojin,Kim, Yong-Chul
, p. 5383 - 5391 (2011)
Pheophorbide-a, a chlorine based photosensitizer known to be selectively accumulated in cancer cells, was conjugated with anticancer drugs, doxorubicin and paclitaxel in the purpose of selective cancer diagnosis and therapy. Pheophorbide-a was conjugated with anticancer drugs via directly and by the use of selective cleavage linkers in cancer cell. The fluorescence of pheophorbide-a and doxorubicin conjugate by excitation at 420 or 440 nm was greatly diminished possibly by the energy transfer mechanism between two fluorescent groups. However, upon treatment in cancer cells, the conjugate showed to be cleaved to restore each fluorescence of pheophorbide-a and doxorubicin after 48 h of incubation. Also, pheophorbide-a conjugates either with doxorubicin and paclitaxel inhibited the growth of various cancer cells more potently than pheophorbide-a, which displayed very weak inhibitory activity. The results indicated that the pheophorbide-a conjugates with anticancer drugs could be utilized for selective cancer therapy as well as for the fluorescence detection of cancer.
Distribution of chlorophyll- and bacteriochlorophyll-derived photosensitizers in human blood plasma
Dandler, Joerg,Wilhelm, Brigitte,Scheer, Hugo
, p. 182 - 193 (2010)
Chlorophylla and, in particular, bacteriochlorophyll a derivatives are promising candidates for photosensitizers in photodynamic therapy. The distribution of 21 (bacterio)chlorophyll derivatives among human blood plasma fractions was studied by iodixanol gradient ultracentrifugation and in situ absorption spectroscopy. Modifications of the natural pigments involved the central metal (Mg2+, Zn2+, Pd2+, none), the isocyclic ring (closed, open and taurinated), substituents at C-3 (vinyl, acetyl, 1-hydroxyethyl) and C-173 (phytyl ester, free acid). Cellular blood components bound only a small fraction of the pigments. Distribution among low-density lipoproteins (LDL), high-density lipoproteins (HDL) and high-density proteins (HDP) of the plasma was influenced as follows: (1) application in Cremophor EL slightly altered pigment distribution by lipoprotein modification, (2) only very polar pigments with multiple hydrophilic substituents showed substantial HDP binding, (3) the presence of the esterifying alcohol at C-173 caused enrichment in LDL, this was more pronounced with bacteriochlorophylls than with chlorophylls, (4) substituents at C-3 had only little influence on the distribution, (5) Zn2+-complexes were enriched in HDL compared to Mg2+ and Pd2+ complexes, indicating specific binding of the former. Equilibration of pigments among the different fractions was largely complete within 3 h.
Synthesis of Covalently Linked dimeric Derivatives of Chlorophyll a, Pyrochlorophyll a, Chlorophyll b, and Bacteriochlorophyll a
Wasielewski, Michael R.,Svec, Walter A.
, p. 1969 - 1974 (1980)
Bis(chlorophyllide) ethylene glycol diesters were prepared for each of the title compounds.Pheophytins a and b isolated from alfalfa and bacteriochlorophyll a isolated from R.sphaeroides were treated with 80percent aqueous trifluoroacetic acid to yield the corresponding pheorbides.Pyropheophorbide was prepared by a literature procedure.Carbonic anhydride and benzotriazole-1-methanesulfonate activation methods were used in the esterification of the pheophorbides with ethylene glycol at ambient temperature.Each method yielded 75percent+ of the pheophorbide ethylene glycol monoester.These monoesters were treated with equimolar amounts of the corresponding pheophorbide by using benzotriazole-1-methanesulfonate/4-(dimethylamino)pyridine in CH2Cl2 or dicyclohexylcarbodiimide/4-(dimethylamino)pyridine in CH2Cl2 at ambient temperature.Yields of bis-(pheophorbide) ethylene glycol diesters averaged about 50percent for the former method and 70percent for the latter method.Insertion of the magnesium atoms into the a series macrocycles was accomplished with iodomagnesium 2,6-di-tert-butyl-4-methylphenolate, IMgBHT, in CH2Cl2, while the metalation of the b and bacterial series macrocycles was carried out with a mixture of IMgBHT and lithium 2,2,6,6-tetramethylpiperidie in thiophene, all at ambient temperature.Both mono- and dimethalated derivatives were isolated and characterized in each case.
