Methyl Pheophorbide-a Research Articles

Synthesis of pyrazole substituted methyl pheophorbide-a derivatives and their preliminary in vitro cell viabilities

The unique ability of chlorophyll derivatives to accumulate in tumorous tissues and to cause a photodynamic effect under laser radiation has been successively used in photodynamic therapy. In this connection, enormous research on modifications of the peripheral substituents in chlorophyll has shown that the presence and position of the substituents in the chlorin derivatives make a remarkable difference in biological activity. As a result, we directed our attention to synthesize methyl pheophorbide-a derivatives, chlorophyll-a derivatives, possessing heterocyclic aromatic substituents or pyrazole moieties on the peripheral positions and to examine preliminary in vitro effects of these new derivatives on A549 cancer cells for PDT. From our experimental results, it was observed that the biological effect induced by photosensitizers on cancer cells may also depend upon the chemical structure of the photosensitizers.

Photodynamic Inactivation of Staphylococcus auerus by Novel Troponyl Methyl (Pyro)pheophorbides

The novel candidates for PDI are based on methyl pheophorbide-a (MPa) and methyl pyropheophorbide-a (MPPa), isolated from alga Spirulina pacifica, which were linked with tropolone, seven membered cyclic compound by substitution on 3-position. Tropolone, as the substituent of new photosensitizers in this study, has been found to have the following biological activities: antimicrobial activity, cytotoxic effects on various human and murine tumor cell lines, phytogrowth-inhibitory activity, insecticidal effect, metalloprotease inhibition, and antifungal activity on wood rotting fungi. 5,6 Meanwhile, chlorin-based compounds show effective anticancer photodynamic activities. 7 Therefore, the combined compound of novel photosensitizers as PDT and the tropolones as antimicrobials were prepared to see the dual function activities. In this paper, we wish to report the preliminary results of the research on Gram-positive bacterial cell S. aureus (strain KC1927) using troponyl methyl (pyro)pheophorbides. Experiments were carried out in order to determine the antibacterial photodynamic activities of newly synthesized troponyl methyl (pyro)pheophorbides. The data presented in Table 2 and Figures 1-2 show that the illumination of S. aureus cells which had been exposed to troponyl methyl (pyro)pheophorbide derivatives caused a considerable decrease cell survival, comparing to control conditions. Our findings clearly demonstrate that newly synthesized troponyl methyl (pyro)pheophorbide derivatives (2, 3 and 5, 6) exhibit significant antimicrobial photodynamic activities against Gram-positive bacterium S. aureus activity at micromolar concentrations. Kill rate of bacterial cells increased in proportion to the increase of the incubation time and were depending on

Mono‐(l)‐aspartylchlorin‐e6†‡

Mono-(L)-aspartylchlorin-e6 (also known as Talaporfin, NPe6, MACE, and most recently LS-11) is a potent sensitizer for photodynamic therapy that is currently undergoing clinical trials. Using a combination of unambiguous partial synthesis from pheophytin-a and methyl pheophorbide-a, NMR spectroscopy, and single crystal X-ray diffraction, the structure of mono-(L)-aspartylchlorin-e6 is definitively shown to be the isomer in which the aspartyl residue is attached at the 15(2)-side chain position. This conclusion is contrary to earlier assumptions, but affirms the conclusions of a study based on NMR spectroscopy; a rationale for the unique formation of the 15(2)-aspartyl derivative is proposed.

Synthesis of Purpurin Imide Derivatives by Modification of Peripheral Functional Groups of Methyl Pheophorbide-a

A series of novel purpurin-18 imide derivatives exhibiting long wavelength absorption and amphiphilicity were obtained from methyl pheophorbide-a (MPa) by modification of the peripheral functional groups. The vinyl group at 3-position was oxidized with OsO4 and NaIO4 to form the formyl group and the Grignard reaction of this aldehyde with the alkyl magnesium bromide was carried out to give the corresponding 3-(1-hydroxylalkyl) pheophorbide-a. The E-ring of these chlorines was converted into anhydride ring to give purpurin derivatives by air oxidation. The trans-32-alkyl purpurin derivatives were obtained by dehydration of hydroxyl group at 31-position. The N-hydroxyl purpurin imide was generated by treatment of the anhydride ring with hydroxylamine hydrochloride. The 31-alkylacyl-N-hydroxyl purpurin imides were obtained by oxidation of hydroxyl group at 31-position. The acylation of N-hydroxyl group was completed to afford N-acyloxy purpurin imides. The photocytoxicity of several compounds in vitro were tested.

Energy and electron transfer properties of methyl pheophorbide- a in zinc porphyrin-pheophorbide dyads

A series of ortho-, meta- and para-substituted zinc porphyrin-pheophorbide dyads were synthesized directly from methyl pheophorbide-a by trans-esterification of β-keto methyl ester with hydroxymethyl substituted porphyrins. Quantitative energy transfer occurred from the excited zinc porphyrin to the pheophorbide. The excited state of the pheophorbide was quenched by an electron transfer reaction from the zinc porphyrin that was found to depend both on the distance between chromophores and the polarity of solvent.

Transesterification of the α-keto ester in methyl pheophorbide- a

Transesterification of the α-keto methyl ester in methyl pheophorbide-a proceeds smoothly under neutral conditions, allowing the preparation of a variety of models such as steroid-pheophorbide, pyromellitimide-pheophorbide, thymidine-pheophorbide, pheophorbide dimer, and porphyrin-pheophorbide.

CHLORIN AND PORPHYRIN DERIVATIVES AS POTENTIAL PHOTOSENSITIZERS IN PHOTODYNAMIC THERAPY

In order to find a photosensitizer with better optical properties and pharmacokinetics than Photofrin II, a series of new photosensitizers related to methyl pheophorbide-a and chlorin-e6 were synthesized. These compounds absorb at substantially longer wavelengths (lambda max 660 nm) than does Photofrin II (630 nm) and show promise for use in photodynamic therapy. Among the porphyrins, we observed that long carbon chain ether derivatives are better photosensitizers than their ester analogs. These sensitizers were tested for in vivo photosensitizing activity vis-a-vis Photofrin II, using the standard screening system of DBA/2 mice bearing transplanted SMT/F tumors. Most of these photosensitizers were found to have better tumoricidal photosensitizing activity than Photofrin II and demonstrated more rapid attenuation of normal tissue photosensitivity with time after administration vis-a-vis Photofrin II.

Partial synthesis of chlorophyll-a from rhodochlorin

A synthesis of chlorophyll-a from a relay degradation product, rhodochlorin dimethyl ester, is described. Key steps involve formation of methyl pheophorbide-a by thallium(III) promoted photocyclization of the corresponding chlorin-6- β-keto-esler, and magnesium(II) insertion using Eschenmoser's BHT method.

Chlorophyll lasers: Stimulated light emission by chlorophylls and Mg-free chlorophyll derivatives

Stimulated emission and lasing have been demonstrated for chlorophyll a, chlorophyll b, and bacteriochlorophyll a as well as for the Mg-free chlorophyll derivatives pheophytin a and methyl pheophorbide a. Population inversion was obtained by optically pumping with an N(2) laser. For the three chlorophylls, lasing was observed for only the (0,0) vibronic region of the S(1) --> S(0) fluorescence band. In contrast, lasing was observed for both the (0,0) and (0,1) vibronic regions of the S(1) --> S(0) fluorescence band of pheophytin a and methyl pheophorbide a. Differences between the lasing behavior of the chlorophylls and the Mg-free derivatives probably reflect differences in aggregation behavior. Laser pulses of duration shorter than the fluorescence lifetimes were generated. This result suggests that stimulated emission must be considered in the interpretation of fluorescence lifetime data for in vitro and in vivo chlorophyll-containing systems.