15664-29-6Relevant articles and documents
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.
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.
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 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.
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.
Amino acid derivatives of pyropheophorbide-a ethers as photosensitizer: Synthesis and photodynamic activity
Meng, Zhi,Shan, Bin,Zhang, Ling,Han, Gui-Yan,Liu, Ming-Hui,Jia, Ning-Yang,Miao, Zhen-Yuan,Zhang, Wan-Nian,Sheng, Chun-Quan,Yao, Jian-Zhong
, p. 623 - 626 (2016)
Ten new water-soluble amino acid conjugates of pyropheophorbide-a ethers 4a-4j were synthesized and investigated for their in vitro photodynamic antitumor activity. The results showed that all compounds exhibited higher phototoxicity and lower dark toxicity against three kinds of tumor cell lines than BPD-MA. In particular, the most phototoxic compound 4d and 4j individually showed IC50 values of 41 nmol/L and 33 nmol/L against HCT116 cell, which represented 7.8- and 9.7-fold increase of antitumor potency compared to BPD-MA, respectively, suggesting that they were promising photosensitizers for PDT applications because of their strong absorption at long wavelength (λmax > 650 nm), high phototoxicity, low dark cytotoxicity and good water-solubility.
Effects of noncovalently bound quinones on the ground and triplet states of zinc chlorins in solution and bound to de novo synthesized peptides
Mennenga, Anke,Gaertner, Wolfgang,Lubitz, Wolfgang,Goerner, Helmut
, p. 5444 - 5453 (2006)
The Qy absorption band of two chlorophyll derivatives, zinc chlorin e6 (ZnCe6) and zinc pheophorbide a (ZnPheida), in aqueous solution is bathochromically shifted on addition of quinones, e.g., 1,4-benzoquinone (BQ), with a corresponding shift of the fluorescence band. This is due to a complex formation of zinc chlorins induced by BQs and subsequent rearrangement. The time-resolved absorption spectra after laser pulse excitation show triplet quenching of the pigments by BQ and other quinones via electron transfer. The effects of electron transfer to noncovalently bound BQs were also studied with de novo synthesized peptides, into which ZnCe6 and ZnPheida were incorporated as model systems for the primary steps of photosynthetic reaction centers. Whereas the photophysical properties are similar to those of the unbound zinc chlorins, no BQ-mediated complex formation was observed. the Owner Societies.
Design and synthesis of novel water-soluble amino acid derivatives of chlorin p6 ethers as photosensitizer
Zhang, Xingjie,Meng, Zhi,Ma, Zhiqiang,Liu, Junhong,Han, Guiyan,Ma, Fujia,Jia, Ningyang,Miao, Zhenyuan,Zhang, Wannian,Sheng, Chunquan,Yao, Jianzhong
, p. 247 - 249 (2019)
Eight new water-soluble amino acid conjugates 6a-h of chlorin p6 ethers (5a-d) were synthesized and preliminarily investigated for their in vitro PDT antitumor activity and structure-activity relationship (SAR). The results showed that all compounds exhibited much higher phototoxicity against tumor cells than talaporfin. SAR analysis indicated that PDT antitumor effect enhanced with the increase of carbon chain length of alkoxyl ether bonds at 31-position, and L-aspartic acid was superior to L-glutamic acid. In particular, the IC50 values of most phototoxic compound 6d were 0.20 μmol/L against A549 cell and 0.41 μmol/L against B16-F10 cell, which individually represented 31- and 24-fold increase of antitumor potency compared to talaporfin, suggesting that it was a promising candidate photosensitizer (PS) for PDT applications due to its strong absorption at long wavelength, high phototoxicity, low dark cytotoxicity and good water-solubility.
Semi-synthesis and HPLC analysis of (bacterio)chlorophyllides possessing a propionic acid residue at the C17-position
Teramura, Misato,Tamiaki, Hitoshi
, p. 423 - 436 (2018)
Various chlorophyll and bacteriochlorophyll derivatives possessing a magnesium or zinc atom at the central position and a free carboxylic acid group at the C172-position, also known as (bacterio)chlorophyllides, were synthesized through a combination of organic synthesis techniques and enzymatic steps. The semi-synthetic (bacterio)chlorophyllides were purified and analyzed using reversed-phase high-performance liquid chromatography with UV-vis spectroscopy and mass spectrometry. These free propionic acid-containing chlorophyllous pigments can be useful research materials for the study of (bacterio)chlorophyll metabolisms.
Novel chlorin e4 derivative, pharmaceutically acceptable salt thereof, and preparation methods and application of novel chlorin e4 derivative and thepharmaceutically acceptable salt thereof
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Page/Page column 14, (2021/10/27)
The invention belongs to the technical field of medicines, and relates to a novel chlorin e4 derivative and pharmaceutically acceptable salts thereof, and preparation methods and application of the novel chlorin e4 derivative and thepharmaceutically acceptable salt thereof. The chlorin e4 derivative comprises a structure shown as a general formula I and an optical isomer contained in the structural general formula I; according to the preparation method, 17-propionyl or 13-formyl in chlorin e4 and amino acid are subjected to peptide formation and/or 3-vinyl etherification. The chlorin e4 derivative and the pharmaceutically acceptable salt thereof can be applied as a photodynamic antitumor drug. Compared with the existing similar photosensitizer talaporfin which is clinically applied, the chlorin e4 derivative disclosed by the invention has the advantages of strong photodynamic antitumor activity, high dark toxicity-light toxicity ratio and the like; the derivative can be used for preparing novel photodynamic antitumor drugs including photodynamic cancer treatment drugs, drugs for photodynamic treatment of benign vascular diseases such as age-related macular degeneration and nevus flammeus and drugs for photodynamic treatment of condyloma acuminata.
