Showing papers on "Protoporphyrin IX published in 2003"
Journal Article•
TL;DR: This study supports the validity and potential utility of (1)O(2) luminescence measurement as a dosimetric tool for PDT, as well as confirming the likely role of porphyrin-based PDT.
Abstract: Singlet oxygen ((1)O(2)) is widely believed to be the major cytotoxic agent involved in photodynamic therapy (PDT). We showed recently that measurement of the weak near infrared luminescence of (1)O(2) is possible in cells in vitro and tissues in vivo. Here, we investigated the relationship between the integrated luminescence signal and the in vitro PDT response of AML5 leukemia cells sensitized with aminolevulinic acid-induced protoporphyrin IX (PpIX). Sensitized cell suspensions were irradiated with pulsed 523 nm laser light at average fluence rates of 10, 25, or 50 mWcm(-2) and, (1)O(2) luminescence measurements were made throughout the treatment. Cell survival was measured with either propidium iodide-labeled flow cytometry or colony-forming assay. The PpIX concentration in the cells, the photobleaching, and the pO(2) in the cell suspensions were also monitored. There were large variations in cell survival and (1)O(2) generation in different experiments due to different controlled treatment parameters (fluence and fluence rate) and other uncontrolled factors (PpIX synthesis and oxygenation). However, in all of the cases, cell kill correlated strongly with the cumulative (1)O(2) luminescence and allowed direct estimation of the (1)O(2) per cell required to achieve a specific level of cell kill. This study supports the validity and potential utility of (1)O(2) luminescence measurement as a dosimetric tool for PDT, as well as confirming the likely role of (1)O(2) in porphyrin-based PDT.
172 citations
TL;DR: Both dendrimer porphyrins with either 32 quaternary ammonium groups or 32 carboxylic groups had far lower dark toxicity as compared with PIX, demonstrating their highly selective photosensitizing effect in combination with a reduced systemic toxicity.
161 citations
TL;DR: HAL is an excellent precursor for PpIX synthesis in bladder cancer and with the 2+2 hour topical administration condition it yielded the highest Ppix fluorescence intensity and fluorescence contrast between normal and malignant urothelial cells.
132 citations
TL;DR: A review of the biosynthesis of chlorophylls and bacteriochlorophyLLs from protoporphyrin IX with 235 references is discussed.
116 citations
TL;DR: New light-activated antimicrobial materials with a potentially wide range of possible uses in civilian settings were synthesized by the grafting of protoporphyrin IX and zinc protoporalin IX to nylon fibers, which showed increased antimicrobial activity against S. aureus with increasing exposure time.
Abstract: New light-activated antimicrobial materials with a potentially wide range of possible uses in civilian settings were synthesized by the grafting of protoporphyrin IX and zinc protoporphyrin IX to nylon fibers. These fibers were shown to be active against Staphylococcus aureus at light exposures of 10,000 lux and greater and against Escherichia coli at 60,000 lux. They were ineffective against both strains in the absence of light. At 40,000 lux, these fibers showed increased antimicrobial activity against S. aureus with increasing exposure time. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 2297–2303, 2003
103 citations
TL;DR: It can be supposed that topical use of ester derivatives with longer chains (C(6) or C(8)) is an interesting proposal to optimize topical 5-ALA-PDT.
91 citations
TL;DR: Repeated, not single, ALA treatment without illumination may cause deleterious effects to the liver, which are mediated by oxygen radicals and inhibited by an antioxidant.
82 citations
Patent•
29 Oct 2003
TL;DR: In this article, a method for detecting and treating rapidly growing exogenous cells, such as Protista, or parasites, that preferentially accumulate a photoactivatable porphyrin in which 5-aminolevulinic acid or precursor thereof is administered to the patient, or contacted to the exogeneous cells, in an amount sufficient to induce synthesis fluorescence and/or photosensitizing concentrations of a protoporphyryrin IX in the exogenous cells, followed by exposure of the exogene cells to light of photoactivating wavelengths.
Abstract: Methods of detecting and treating rapidly growing exogenous cells, such as Protista, or parasites, that preferentially accumulate a photoactivatable porphyrin in which 5-aminolevulinic acid or precursor thereof is administered to the patient, or contacted to the exogenous cells, in an amount sufficient to induce synthesis fluorescence and/or photosensitizing concentrations of a protoporphyrin IX in the exogenous cells, followed by exposure of the exogenous cells to light of photoactivating wavelengths.
80 citations
TL;DR: Results confirm that the formation of photoprotopor-phyrin is a photo-oxidation process and that no photobleaching takes place in the absence of oxygen.
Abstract: Photodynamic therapy (PDT) has developed into an important new clinical treatment for cancer during the past 30 years. The method is non-invasive and based on the photochemical activity of a photosensitising agent present in cells and tissues. In so-called ALA-PDT, protoporphyrin IX (Pp IX) is induced from aminolaevulinic acid (ALA) applied topically or systemically. It has been shown that Pp IX is photodegraded by a photo-oxidation process and that its photoproducts have a characteristic absorption band around 670 nm, as observed both in solution and in cells incubated with ALA. In this study, the involvement of oxygen in the photobleaching process was verified by studying the effect of oxygen depletion using the freeze–pump–thaw (FPT) method. A solution of Pp IX in dimethylformamide (DMF) was exposed to light in the wavelength region 600–700 nm (peak centred at 620 (±25) nm) both in the presence and in the absence of oxygen. The bleaching process was observed by absorbance and fluorescence measurements. Photobleaching was observed in the presence of oxygen, as verified by the build-up of a photoproduct absorbing at 670 nm. When the sample was deoxygenated with the FPT method, the photoproduct absorption peak at 670 nm was missing. These results confirm that the formation of photoprotopor-phyrin is a photo-oxidation process and that no photobleaching takes place in the absence of oxygen. When comparing our results to the studies carried out by N2 bubbling, the N2 bubbling seems to be insufficient to remove the oxygen completely from the solution.
77 citations
TL;DR: In situ light dosimetry was used to adjust the fluence rate measured within the esophagus for individual animals and monitored protoporphyrin IX (PpIX) fluorescence photobleaching simultaneously, and it was found that higher PpIX fluorescence photography rates corresponded with more epithelial damage, whereas lower rates corresponding with no response.
Abstract: Experimental therapies for Barrett's esophagus, such as 5-aminolevulinic acid (ALA)–based photodynamic therapy (PDT), aim to ablate the premalignant Barrett's epithelium. However, the reproducibility of the effects should be improved to optimize treatment. Accurate irradiation with light of a proper wavelength (633 nm), fluence and fluence rate has shown to be critical for successful ALA-PDT. Here, we have used in situ light dosimetry to adjust the fluence rate measured within the esophagus for individual animals and monitored protoporphyrin IX (PpIX) fluorescence photobleaching simultaneously. Rats were administered 200 mg kg–1 ALA (n = 14) or served as control (n = 7). Animals were irradiated with an in situ measured fluence rate of 75 mW cm–2 and a fluence of 54 J cm–2. However, this more accurate method of light dosimetry did not decrease the variation in tissue response. Large differences were also observed in the dynamics of PpIX fluorescence photobleaching in animals that received the same...
75 citations
TL;DR: The distribution of protoporphyrin IX (PpIX) induced in 7 different tissues by these drugs was determined either by spectrofluorometric measurements with an optical fibre probe or by chemical extraction of PpIX from the tissues.
Abstract: Aminolevulinic acid (ALA), ALA methylester (ALA-Me) and ALA hexylester (ALA-Hex) were topically applied for 5 and 20 hr, respectively, on normal skin of mice. The distribution of protoporphyrin IX (PpIX) induced in 7 different tissues by these drugs was determined either by spectrofluorometric measurements with an optical fibre probe or by chemical extraction of PpIX from the tissues. The results from these 2 types of measurements were compared. Both methods showed that ALA and the esters induced similar amounts of PpIX at the skin spot where they were applied and that the esters produced much less PpIX at remote skin spots (i.e., spots outside the location where the drugs were applied) than ALA did, notably after 20 hr application. After 20 hr of drug application ALA produced much more PpIX in liver, intestine and lungs than the esters did. In contrast with the direct fluorescence measurements, the extraction method showed detectable amounts of PpIX in liver, intestine and lung after application of the esters, notably of ALA-Me. The discrepancy is probably related to the fact that the pigmented tissues absorb light and, therefore, the direct fluorescence readings are misleading. Notably in the liver, which contains high concentration of light-absorbing pigments, very weak direct fluorescence was seen. In no case there was any accumulation of PpIX in muscle tissue nor in brain. The esters seem to penetrate less into the circulation than ALA, and PpIX formed by them in the skin is faster cleared than PpIX formed from ALA. This is also true after oral and i.p. administration of the drugs. © 2002 Wiley-Liss, Inc.
TL;DR: Single turnover experiments with oxygen-loaded HemF under anaerobic conditions demonstrated electron acceptor function for oxygen during the oxidative decarboxylation reaction with the concomitant formation of H2O2.
TL;DR: Results suggest that PBR, in addition to its role in cholesterol and coproporphyrinogen III transport, is also directing the mitochondrial PPIX import, a function that can be ascribed to the 18kDa PBR protein alone.
TL;DR: This proposal is strengthened by the fact that the only tested metal ion with a lower distortion energy than free-base porphyrin (Cd2+) is an inhibitor of ferrochelatase, and it costs even less energy to tilt a doubly deprotonated porphine2– molecule.
Abstract: Ferrochelatase is the terminal enzyme in haem biosynthesis, i.e. the enzyme that inserts a ferrous ion into the porphyrin ring. Suggested reaction mechanisms for this enzyme involve a distortion of the porphyrin ring when it is bound to the enzyme. We have examined the energetics of such distortions using various theoretical calculations. With the density functional B3LYP method we calculate how much energy it costs to tilt one of the pyrrole rings out of the porphyrin plane for an isolated porphyrin molecule without or with a divalent metal ion in the centre of the ring. A tilt of 30 degrees costs 65-130 kJ/mol for most metal ions, but only approximately 48 kJ/mol for free-base (neutral) porphine. This indicates that once the metal is inserted, the porphyrin becomes stiffer and flatter, and therefore binds with lower affinity to a site designed to bind a distorted porphyrin. This would facilitate the release of the product from ferrochelatase. This proposal is strengthened by the fact that the only tested metal ion with a lower distortion energy than free-base porphyrin (Cd(2+)) is an inhibitor of ferrochelatase. Moreover, it costs even less energy to tilt a doubly deprotonated porphine(2-) molecule. This suggests that the protein may lower the acid constant of the pyrrole nitrogen atoms by deforming the porphyrin molecule. We have also estimated the structure of the protoporphyrin IX substrate bound to ferrochelatase using combined quantum chemical and molecular mechanics calculations. The result shows that the protein may distort the porphyrin by approximately 20 kJ/mol, leading to a distinctly non-planar structure. All four pyrrole rings are tilted out of the porphyrin mean plane (1-16 degrees ) but most towards the putative binding site of the metal ion. The predicted tilt is considerably smaller than that observed in the crystal structure of a porphyrin inhibitor.
TL;DR: Assembly of the entire heme biosynthetic pathway in a three-plasmid system and overexpression of the corresponding genes with Escherichia coli as a host yielded remarkable porphyrin production levels, which may indicate that heme has a regulatory impact on the iron uptake of E. coli or that the ferrochelatase is inactive in vivo due to an incompatible enzyme interaction.
Abstract: Due to their spectroscopic properties porphyrins are of special interest for a variety of applications, ranging from drug development or targeting to material sciences and chemical and biological sensors. Since chemical syntheses are limited in terms of regio- and stereoselective functionalization of porphyrins, a biosynthetic approach with tailored enzyme catalysts offers a promising alternative. In this paper, we describe assembly of the entire heme biosynthetic pathway in a three-plasmid system and overexpression of the corresponding genes with Escherichia coli as a host. Without further optimization, this approach yielded remarkable porphyrin production levels, up to 90 μmol/liter, which is close to industrial vitamin B12 production levels. Different combinations of the genes were used to produce all major porphyrins that occur as intermediates in heme biosynthesis. All these porphyrin intermediates were obtained in high yields. The product spectrum was analyzed and quantified by using high-performance liquid chromatography. Intriguingly, although protoporphyrin IX could be produced at high levels, overexpressed Bacillus subtilis ferrochelatase could not convert this substrate appreciably into heme. However, further investigation clearly revealed a high level of expression of the ferrochelatase and a high level of activity in vitro. These results may indicate that heme has a regulatory impact on the iron uptake of E. coli or that the ferrochelatase is inactive in vivo due to an incompatible enzyme interaction.
TL;DR: Investigation of the subcellular localization of two types of ferrochelatase (CsFeC1 and CsFeC2) in cucumber demonstrated that in cucumbers both CsF1 andCsF2 are solely targeted into plastids, but not into mitochondria, implying the reconsideration of mitochondrial heme biosynthesis in higher plants.
Abstract: It is widely believed that ferrochelatase (protoheme ferrolyase, EC 4.99.1.1), which catalyzes the insertion of ferrous ion into protoporphyrin IX to form protoheme, exists in both plastids and mitochondria of higher plants. By in vitro import assay with isolated pea (Pisum sativum L.) organelles, it has been proposed that one of two isoforms of ferrochelatase (type 1) is dual-targeted into both plastids and mitochondria, and functions for heme biosynthesis in the both organelles. Recently, however, mitochondrial targeting of ferrochelatase is being disputed since pea mitochondria appeared to accept a variety of chloroplast proteins including the type-1 ferrochelatase of Arabidopsis thaliana (L.) Heynh. To clarify the precise subcellular localization of ferrochelatase in higher plants, here we investigated the subcellular localization of two types of ferrochelatase (CsFeC1 and CsFeC2) in cucumber (Cucumis sativus L.). In cotyledons, a significant level of specific ferrochelatase activity was detected in thylakoid membranes, but only a trace level of activity was detectable in mitochondria. Western blot analysis with specific antibodies showed that anti-CsFeC2 antiserum cross-reacted with plastids in photosynthetic and non-photosynthetic tissues. Anti-CsFeC1 did not cross-react with mitochondria, but CsFeC1 was clearly detectable in plastids from non-photosynthetic tissues. In situ transient-expression assays using green fluorescent protein demonstrated that, as well as CsFeC2, the N-terminal transit peptide of CsFeC1 targeted the fusion protein solely into plastids, but not into mitochondria. These results demonstrated that in cucumber both CsFeC1 and CsFeC2 are solely targeted into plastids, but not into mitochondria. Screening of a cucumber genomic or cDNA library did not allow any other ferrochelatase homologous gene to be isolated. The data presented here imply the reconsideration of mitochondrial heme biosynthesis in higher plants.
TL;DR: In 5‐aminolaevulinic acid (ALA)‐photodynamic therapy (PDT), the prodrug ALA is endogenously converted to the active sensitizer protoporphyrin IX (PpIX), while further conversion of PpIX to haem requires iron.
Abstract: SummaryBackground In 5-aminolaevulinic acid (ALA)-photodynamic therapy (PDT), the prodrug ALA is endogenously converted to the active sensitizer protoporphyrin IX (PpIX), while further conversion of PpIX to haem requires iron.
Objectives To explore the potential of the iron chelator desferrioxamine (DFO) to enhance PpIX levels and phototoxicity in ALA-PDT.
Methods A series of six doses of 2% ALA solution was iontophoresed into the healthy skin of each ventral forearm of 10 volunteers. One arm was pretreated with 20% DFO in aqueous cream, while the control arm received aqueous cream alone, for 16 h. At 5 h following iontophoresis, skin-surface PpIX fluorescence was measured, following which the forearms were simultaneously irradiated with 100 J cm−2 broadband red light. The phototoxic reaction was assessed at 24 h postirradiation as the minimal phototoxic dose (MPD) and with quantification of erythema. Next, eight patients with two superficial basal cell carcinomas or two plaques of Bowen's disease of similar appearance received 20% ALA topically to one lesion and 20% ALA with 20% DFO to the other, for 3 h. Skin-surface PpIX fluorescence was measured at 5 h, following which lesions were irradiated with 100 J cm−2 broadband red light.
Results In healthy skin, PpIX fluorescence increased with increasing ALA dose at DFO-treated and untreated sites (P < 0·0005); PpIX fluorescence peak values were consistently higher in DFO-treated compared with control sites (P < 0·02). Erythema also correlated with ALA dose (P < 0·0005), but a significant difference between active and control sites occurred only at low ALA dose (P < 0·05). The median MPD appeared lower at the DFO-treated sites, at 6 mC vs. 12 mC (P = 0·06). In contrast, in lesional skin there was no consistent difference in PpIX fluorescence levels between those treated with and without DFO.
Conclusions While iron chelation augmented ALA-PDT phototoxicity in normal skin, this occurred only at low ALA dose. Addition of DFO does not appear to confer additional benefit in ALA-PDT of nonmelanoma skin cancers.
TL;DR: The results suggest that the autofluorescence in oral SCC correlates with the progression of lesions, and that fluorescent substances such as protoporphyrin are produced in association with the cancerous tissue.
TL;DR: It is demonstrated that Zn2+, which is commonly used as substrate in assays of the ferrochelatase reaction, and Cd2+, an inhibitor of the enzyme, bind to the invariant amino acids His183 and Glu264 and water molecules, all located within the porphyrin binding cleft.
Abstract: Ferrochelatase, the terminal enzyme in heme biosynthesis, catalyses metal insertion into protoporphyrin IX. The location of the metal binding site with respect to the bound porphyrin substrate and the mode of metal binding are of central importance for understanding the mechanism of porphyrin metallation. In this work we demonstrate that Zn2+, which is commonly used as substrate in assays of the ferrochelatase reaction, and Cd2+, an inhibitor of the enzyme, bind to the invariant amino acids His183 and Glu264 and water molecules, all located within the porphyrin binding cleft. On the other hand, Mg2+, which has been shown to bind close to the surface at 7 A from His183, was largely absent from its site. Activity measurements demonstrate that Mg2+ has a stimulatory effect on the enzyme, lowering KM for Zn2+ from 55 to 24 µM. Changing one of the Mg2+ binding residues, Glu272, to serine abolishes the effect of Mg2+. It is proposed that prior to metal insertion the metal may form a sitting-atop (SAT) complex with the invariant His-Glu couple and the porphyrin. Metal binding to the Mg2+ site may stimulate metal release from the protein ligands and its insertion into the porphyrin.
TL;DR: It appears that ALA-H could achieve similar or slightly better results than ALA with respect to PpIX production and photoinactivation of cells, although a 10 times lower concentration of ALA -H was used.
TL;DR: In this article, a new method for quantification of both free and total SO 2 is described, which gives a linear range up to 9.0μg −1 and a detection limit of 0.15μg−ml −1 for SO 2.
Abstract: A new method for quantification of both free and total SO 2 is described. Poly[Ni-(protoporphyrin IX)] (NiPPIX) film at submonolayer-level-modified glassy carbon electrodes showed an important catalytic effect for the oxidation of SO 2 . This modified electrode is an useful tool in chemical analysis when it is incorporated to an amperometric detector in a flow or in a stirred system. The method gives a linear range up to 9.0 μg ml −1 and a detection limit of 0.15 μg ml −1 for SO 2 . The described method is simple and non-expensive. Surface coating is highly stable under hydrodynamic conditions in the flow cell.
TL;DR: In this paper, zinc protoporphyrin IX and poly(acrylic acid) (PAA) scaffolds were used to grafted to nylon-6,6 films via an ethylene diamine bridge and its zinc salt.
Abstract: Protoporphyrin IX and zinc protoporphyrin IX were grafted to the surface of nylon-6,6 films via an ethylene diamine bridge and a poly(acrylic acid) (PAA) scaffold. X-ray photoelectron spectroscopy showed that approximately 57% of the nylon surface was covered by PAA and approximately 6% of the carboxylic acid groups in PAA were grafted to the ethylene diamine derivative of protoporphyrin IX or its zinc salt.
TL;DR: These data demonstrate that, as for Haemophilus influenzae, reliance on captured iron and on exogenous porphyrin is manifest as an absolute growth requirement for heme.
Abstract: The porphyrin requirements for growth recovery of Porphyromonas gingivalis in heme-depleted cultures are investigated. In addition to physiologically relevant sources of heme, growth recovery is stimulated by a number of noniron porphyrins. These data demonstrate that, as for Haemophilus influenzae, reliance on captured iron and on exogenous porphyrin is manifest as an absolute growth requirement for heme. A number of outer membrane proteins including some gingipains contain the hemoglobin receptor (HA2) domain. In cell surface extracts, polypeptides derived from HA2-containing proteins predominated in hemoglobin binding. The in vitro porphyrin-binding properties of a recombinant HA2 domain were investigated and found to be iron independent. Porphyrins that differ from protoporphyrin IX in only the vinyl aspect of the tetrapyrrole ring show comparable effects in competing with hemoglobin for HA2 and facilitate growth recovery. For some porphyrins which differ from protoporphyrin IX at both propionic acid side chains, the modification is detrimental in both these assays. Correlations of porphyrin competition and growth recovery imply that the HA2 domain acts as a high-affinity hemophore at the cell surface to capture porphyrin from hemoglobin. While some proteins involved with heme capture bind directly to the iron center, the HA2 domain of P. gingivalis recognizes heme by a mechanism that is solely porphyrin mediated.
TL;DR: There are data suggesting that aminolevulinic acid/photodynamic therapy may also be beneficial in acne vulgaris, verrucae, psoriasis, mycosis fungoides, and human papillomavirus.
Abstract: Photodynamic therapy is a non-invasive technique used in the treatment of skin diseases which has various advantages, one being the ability to localize treatment to the area being treated, which is common among most photosensitizers. Aminolevulinic acid is a prodrug that is metabolized intracellularly to form the photosensitizing molecule protoporphyrin IX (PpIX). When PpIX is activated by light, cytotoxic reactive oxygen species and free radicals are generated. This phototoxic effect may cause malignant and non-malignant hyperproliferative tissue to be destroyed, to decrease in size, and to eventually disappear. The application of topical aminolevulinic acid 20% followed by the use of a blue light photodynamic therapy illuminator is indicated in the US for the treatment of non-hyperkeratotic actinic keratoses of the face or scalp. There are data suggesting that aminolevulinic acid/photodynamic therapy may also be beneficial in acne vulgaris, verrucae, psoriasis, mycosis fungoides, and human papillomavirus. This treatment modality has also proven effective in the management of skin cancer such as, Bowen disease and basal cell carcinoma. Further experience in the use of photodynamic therapy will help define its utility in the management of actinic keratosis and other dermatoses.
TL;DR: In trophozoite lysate-mediated heme polymerization assays, SnPPIX, GaPPIX and GaDPIX exerted potent inhibitory activity similar to that of artemisinin and chloroquine.
Abstract: The in vitro antimalarial activity against Plasmodium falciparum and heme polymerization were evaluated for ten metalloporphyrins: gallium protoporphyrin IX (GaPPIX), sodium salt of gallium protoporphyrin IX, silver protoporphyrin IX, palladium protoporphyrin IX, cobalt protoporphyrin IX, manganese protoporphyrin IX, tin protoporphyrin IX (SnPPIX), chromium protoporphyrin IX, gallium deuteroporphyrin IX (GaDPIX) and gallium hematoporphyrin IX. Metalloporphyrins inhibited parasite growth with 50% inhibitory concentrations (IC50) ranging from 15.5 μM to 190 μM. In trophozoite lysate-mediated heme polymerization assays, SnPPIX, GaPPIX and GaDPIX exerted potent inhibitory activity similar to that of artemisinin and chloroquine.
TL;DR: Drugs coupled to Gly-Gly/Gly-Pro derivatives of 5-aminolevulinic acid (ALA) esters may selectively target defined cells in human cancer, depending on specific cellular activating pathways expressed by the cells.
TL;DR: ALA-induced PPIX levels and showed improved phototoxicity compared with the references ALA hydrochloride 1, ALA hexylester hydro chloride 3 and ALA benzylester Hydrochloride 4 are promising compounds for PD and PDT.
Abstract: Photodetection (PD) and photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) accumulation are approaches to detect and treat dysplasia and early cancer in the gastrointestinal tract and in the urinary bladder. Because ALA-induced PPIX production is limited, we synthesized ALA ester hydrochlorides 3-22 and tested them in two different in vitro models (gastrointestinal tract: HT29-CCD18; urinary bladder: J82-UROTSA). PPIX accumulation after incubation with 0.12 mmol/L for 3 h and PPIX accumulation as a function of different incubation times were measured using flow cytometry. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to check cellular dark toxicity. Phototoxicity after irradiation was tested. ALA nonafluorohexylester hydrochloride 11, ALA thiohexylester hydrochloride 13 and ALA dibenzyldiester dihydrochloride 19 induced appreciably increased PPIX levels and showed improved phototoxicity compared with the references ALA hydrochloride 1, ALA hexylester hydrochloride 3 and ALA benzylester hydrochloride 4. Thus, the new compounds 11, 13 and 19 are promising compounds for PD and PDT.
TL;DR: In this article, a review of the biosynthesis of chlorophylls and bacteriochlorophyll from protoporphyrin IX with 235 references is presented, and the literature on the enzymes magnesium chelatase, S-adenosyl-L-methionine:magnesium protoprorin IX O-methyltransferase, magnesium-protoporphyrins IX monomethyl ester oxidative cyclase, protochlorophyllide oxidoreductase, chlorophyLLide 8-vinyl reductase, and chlorophy
Abstract: Covering: 1989 to 2002. Previous review: Nat. Prod. Rep., 1989, 6, 171
A review of the biosynthesis of chlorophylls and bacteriochlorophylls from protoporphyrin IX with 235 references. The literature on the enzymes magnesium chelatase, S-adenosyl-L-methionine:magnesium protoporphyrin IX O-methyltransferase, magnesium-protoporphyrin IX monomethyl ester oxidative cyclase, protochlorophyllide oxidoreductase, chlorophyll synthase, bacteriochlorophyll synthase, protochlorophyllide 8-vinyl reductase and chlorophyll a oxidase from 1989 is discussed.
TL;DR: In this paper, the 1,3-Dipolar cycloaddition mechanism of the formation of 1′-pyrazolinyl derivatives is discussed, and a mixture of mono-and di-substituted pyrazolin analogs are isolated as individual products.
TL;DR: The effect of porphyrins on heme proteins should be given due consideration in elucidating the details of the mechanism of p Morphyrin actions in therapy.
Abstract: Two important porphyrins, protoporphyrin IX and hematoporphyrin IX, derivatives of which form the basis of photosensitization in the photodynamic therapy of cancer treatment, interact with two physiologically important heme proteins hemoglobin and myoglobin. The extent and modality of these interactions vary with the state of aggregation of the two porphyrins. Upon binding with these proteins, both the drugs change the protein conformations and release the heme-bound oxygen from the oxyproteins. At the same time, the peroxidase activities of these proteins are potentiated due to the protein-porphyrin complexation, as is found in case of horseradish peroxidase also. The effect of porphyrins on heme proteins should be given due consideration in elucidating the details of the mechanism of porphyrin actions in therapy.