Search

Summary Background Retinoblastoma is the most common malignant intraocular tumor in children. The current treatment gives a good vital prognostic but there are several drawbacks to the arsenal of “classical antitumoral” therapies. Photodynamic therapy (PDT) could be an exciting non-toxic and non-mutagenic alternative protocol. Method In this paper, we report about the screening of the in vitro photocytotoxicity of hydrophenylporphyrins and chlorins and their glycoconjugated derivatives in a human retinoblastoma cell line (Y79) and for comparison in a colorectal adenocarcinoma cell line (HT29). Results Despite lower photodynamic activity than that observed for hydroxylated photosensitizers, in particular Foscan® glycoconjugated derivatives display phototoxicity (IC50 2.4–0.05 μM ±10%) against Y79 cells with examples of significant intrinsic cytotoxicity. Amongst them the triglucosyl porphyrin 10 is highly photocytotoxic (IC50 0.9 μM ±10%) but is fully devoid of cytotoxicity (IC50 > 15 μM). The photoactivity is highly modulated by the presence of a diethyleneglycol spacer between the chromophore and the glycoside (compounds 14–17, IC50 0.5, 0.6, 0.05 and 0.35 μM ±10%) and by the anomeric configuration of the sugar (compound 15 and 17, IC50 0.6 and 0.05 μM ±10% respectively). One of the main problems for the use of Foscan® is its poor solubility which might be improved by glycoconjugation. Moreover Foscan has been shown to induce necrosis after PDT leading to a possible ulceration of surrounding tissues unsuitable for a conservative treatment. A preferential mitochondrial subcellular localization which has been previously reported for some glycoconjugated photosensitizers could enhance the contribution of apoptosis process. Conclusion Tri-α-O-galactosyl porphyrin 16 is a better candidate than Foscan® for a clinical application of PDT for a conservative therapy of retinoblastoma.

Glucoconjugated tri and tetra(meta-hydroxyphenyl)chlorins have been synthesized in order to explore how glucoconjugation of the macrocycle affects the photoactivity of the molecule. Internalization processes, photosensitizing efficacy of TPC(m-O-GluOH)(3) and TPC(m-O-GluOH)(4), in HT29 human adenocarcinoma cells have been compared to those of tetra(meta-hydroxyphenyl) chlorin (m-THPC, Foscan). The tetra glucoconjugated chlorin, TPC(m-O-GluOH)(4), was found to be poorly internalized and weakly photoactive. In contrast, the asymmetric and more amphiphilic compound TPC(m-O-GluOH)(3), exhibited superior phototoxicity compared to m-THPC. Drug concentration, temperature and sodium azide effects indicated that TPC(m-O-GluOH)(3) internalization partly proceeds via an active receptor-mediated endocytosis mechanism. Cellular uptake appeared as a saturable process and remained 30% lower than for mTHPC. However, a maximum phototoxicity in HT29 cells (survival fraction of 2+/-0.6%) were observed for concentration as low as 2 microM. A 4-fold higher concentration of m-THPC was necessary to observe the same level of photoactivity. This higher phototoxicity has been correlated to a greater mitochondrial affinity. On the basis of these results, work is in progress to further evaluate the potential of glycosylated chlorins in photodynamic therapy (PDT).

The 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (m-THPC) (Foscan) is a photosensitizer used in the photodynamic therapy (PDT) of cancers which is currently under clinical trial. The formation of a m-THPC inclusion complex with dimethyl-beta-cyclodextrin (Me-beta-CD) in solution was demonstrated on the basis of circular dichroism experiments. A 1:2 complex stoichiometry was found and an inclusion constant beta 2 = 2.8(+/- 0.4) x 10(10) M-2 was determined. The formation of such a complex was shown to enhance the m-THPC fluorescence intensity. It could be exploited to improve the sensitivity of the direct m-THPC detection in human plasma. Optimization of the operating conditions shows that the best results were obtained by the addition of 100 microL of a concentrated Me-beta-CD solution (3.2 x 10(-2) M) to 1 mL plasma samples. Compared to the standard conditions, a 90% increase in sensitivity was obtained. The proposed analytical method which showed a linear response function [0-300 ng mL-1 (440 pM)] and a low limit of detection [1.5 ng mL-1 (2 pM) (S/N = 3)] appears, especially due to the absence of metabolism, a simple and specific method suitable for pharmacokinetics studies in patients.

Contexte et objectifs de l'etude: L'identification endoscopique des dysplasies et des carcinomes precoces de l'oesophage est difficile et effectuee au moyen de biopsies etagees systematiques. Cette etude evalue la capacite de la spectroscopie d'autofluorescence UV a detecter ces lesions precoces avec un interet particulier pour l'endobrachyoesophage (EBO). Patients et methodes: Les mesures ont porte sur 24 patients en utilisant une excitation lumineuse a 330 nm. La determination de la distribution spectrale caracteristique de chaque type histologique est faite en utilisant les trois rapports d'intensite de fluorescence. R 1 =I 390nm /I 450nm ; R 2 =I 550nm / I 450nm; R3 =I 390nm /I 550nm . Resultats: Les distributions spectrales relatives a la muqueuse malpighienne oesophagienne saine et a la muqueuse specialisee de l'EBO non dysplasique sont similaires. La presence d'une dysplasie de haut grade ou d'un carcinome intramuqueux se traduit par une modification de la distribution spectrale. L'analyse statistique montre que la modification spectrale associee a la transformation neoplasique est plus forte que les variations intra- et interpatients. Ces resultats ont permis la determination de criteres de discrimination fondes sur les rapports R 1 et R 3 . L'utilisation du rapport R 3 permet de differencier le tissue neoplasique de la muqueuse malpighienne et de la muqueuse de Barrett avec une sensibilite de 86% et une specificite de 95%. Conclusion: La spectroscopie d'autofluorescence UV, en orientant les biopsies, devrait accroitre l'efficacite diagnostique de l'endoscopie conventionnelle.

Fluorescence properties of 5,10,15,20-tetra( m-hydroxyphenyl)chlorin ( m-THPC), a sensitizer used in photodynamic therapy (PDT), were studied in the presence of three native cyclodextrins (CDs) -α, -β, and γ-CD—and two modified cyclodextrins—heptakis (2,6-di- O-methyl) β-CD (Me-β-CD) and heptakis (2- O-hydroxy-propyl) β-CD (HP-β-CD). The CDs studied have been shown to undergo the formation of an inclusion complex with m-THPC, leading to a large enhancement (up to 300 times) of m-THPC fluorescence intensity depending on the CD used. Stoichiometry and association constants have been determined on the basis of the variation of fluorescence intensity. A 1:2 stoichiometry has been found for m-THPC complexes with γ-CD, Me-β-CD, and HP-β-CD. Association constants as high as K = 9.5 × 108 M−2 in the case of m-THPC/2Me-β-CD and K = 2.7 × 109 M−2 in the case of m-THPC/ 2HP-β-CD complex were determined, whereas a lower value ( K = 2.4 × 104 M−2) was found in the case of m-THPC/2γ-CD. Because of the highest fluorescence enhancement (a factor of about 300) observed with Me-β-CD, this compound would be the most suitable to improve the detection of m-THPC in further pharmacokinetics and biodistribution studies.

— It has been recently shown that UVA (320–400 nm) irradiation of DNA in the presence of pyridopsoralens induces the formation of thymine cyclobutane dimers in addition to monoadducts. In this work, we measured the potency of a saturated pyridopsoralen to photosensitize DNA, despite its inability to covalently attach to DNA. First, from spectroscopic fluorescence measurements, we have shown that both analogs, saturated and unsaturated pyridopsoralens, namely 4′,5′-dihydro-7-methyl-pyrido[3,4-clpsoralen (DH-MePyPs) and 7-methylpyrido[3,4-c]psoralen, exhibit a similar global affinity for DNA. Secondly, we demonstrated, by footprinting experiments, that exposure of a DNA sequence to 365 nm UV radiation in the presence of DH-MePyPs results in selective cyclobutane thymine dimerization. Thymines located in the immediate proximity of the 5′-TA-3′ step are exclusively affected and the frequency of this photoprocess depends on flanking sequences. We thus probe a selective thymine dimer photosensitizer. Results are discussed in terms of drug affinity and physical properties of the helix at the binding site.

Photodynamic therapy (PDT) has recently been proposed as a possible indication in the conservative treatment of hereditary retinoblastoma. In order to create photosensitizers with enhanced targeting ability toward retinoblastoma cells, meso- tetraphenylporphyrins bearing one glycodendrimeric moiety have been synthesized. The binding properties to plasma proteins and photodynamic activity of two monodendrimeric porphyrins bearing three mannose units via monoethylene glycol ( 1 ) or diethylene glycol ( 2 ) linkers have been compared to that of the non-dendrimeric tri-substituted derivative [TPP( p -Deg-O-α-ManOH) 3 ]. The dendrimeric structure was found to highly increase the binding affinity to plasma proteins and to modify to some extent plasma distribution. HDL and to a lesser extent LDL have been shown to be the main carriers of dendrimeric and non-dendrimeric compounds. The phototoxicity observed for the two glycodendrimers ( 1 ) and ( 2 ) (LD 50 = 0.5 μM) in Y79 cells is of the same order of magnitude that for TPP( p -Deg-O-α-ManOH) 3 (LD 50 = 0.7 μM), with a similar cellular uptake level for ( 1 ) and a lower for ( 2 ). A serum content increase from 2% to 20% (v/v) in the incubation medium was found to inhibit both cellular uptake and photoactivity of dendrimeric derivatives, whereas those of TPP( p -Deg-O-α-ManOH) 3 remained little affected. Specificities of glycodendrimeric porphyrins, combining a lower cellular uptake together with a higher affinity toward plasma proteins, make these derivatives possible candidates for a vascular targeting PDT.

Summary Purpose Retinoblastoma is the most common primary intraocular tumor in children. In industrialized countries, 95% of patients are cured by chemotherapy and conservative treatments. However, these treatments can increase the risk of secondary tumors in patients with a constitutional alteration of the RB1 gene. Photodynamic therapy represents a nonmutagenic therapeutic approach, and may reduce the incidence of secondary tumors. To study the in vivo efficacy of photodynamic therapy, human retinoblastoma xenografts were established in nude mice. Methods Three xenografted cell lines, RB102-FER, RB109-LAK and RB111-MIL, were characterized and used for therapeutic evaluation. Mice were randomly divided into control and treatment groups with 5–8 mice in each group. Treatment groups received irradiation alone, photosensitizer alone or both in 2 of the 3 models and in the third model, photosensitizer plus irradiation was compared to untreated controls. mTHPC was injected intraperitoneally at a dose of 0.6 mg/kg and verteporfin intravenously at a dose of 1 mg/kg. Illuminations were performed 24 h after mTHPC and 1 h after verteporfin injections. Results A transient but significant response to mTHPC was observed for RB102-FER ( p = 0.03) and a significant response to mTHPC for RB111-MIL ( p −4 ) with partial regression maintained for more than 60 days. No significant difference between the different groups was observed for RB109-LAK, except in the verteporfin plus laser group ( p = 0.01). Conclusions The studies confirmed the suitability of the three xenograft models for the evaluation of photodynamic therapy in retinoblastoma. Our findings suggest that PDT may represent an alternative conservative treatment for these tumors.

The fluorescence properties in solution of the four main aflatoxins, B 1 , B 2 , G 1 and G 2 , in the presence of various cyclodextrin derivatives were studied. A preliminary study was made in order to determine the absorbance and fluorescence spectra, relative quantum fluorescence yields (φ F ), Stokes shifts, E S1 (0-0) energy levels and low-temperature (77 K) data for these aflatoxins. The effect of cyclodextrins on the fluorescence emission was then investigated. A substantial enhancement of the fluorescence emission of aflatoxins with an unsaturated furan ring (B 1 and G 1 ) in the presence of aqueous solutions of α,β-heptakis-di- O -methyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin was observed. Surprisingly, γ-cyclodextrin was inefficient in this respect. Conversely, neither aflatoxin B 2 or G 2 , with a saturated furan ring, showed such an interaction and their emission characteristics remained constant in the presence of cyclodextrins. From a mechanistic point of view, the selectivity of the interaction seems to involve partially a non-inclusion process, because of the high molar ratio of cyclodextrin to aflatoxin needed for the fluorescence enhancement. The correlation between the behaviour in the presence of cyclodextrins and the solvent effect on the furan-unsaturated aflatoxins is discussed.

Glucoconjugated analogues of the meta-hydroxyphenyl porphyrin (m-THPP) and meta-hydroxyphenyl chlorin (m-THPC) has been recently synthesized. The characteristics of their triplet states have been determined with regard to their involvement in the photodynamic (PDT) efficiency. In the case of porphyrin derivatives, triplet quantum yields (Phi(T)) were ranging from 0.42 to 0.55 and triplet life times (tau(T)) from 1 to 5 micros. High reaction rate constants (k(q)) with molecular oxygen (k(q): 1.2-1.6 x 10(9)s(-1)) have been found. The triplet lifetimes of chlorin derivatives were about four times higher than those of porphyrins whereas the Phi(T) and k(q) values remained quite similar. Singlet oxygen yields of glucosylated and non-glucosylated porphyrins and chlorins were not significantly different within experimental errors (Phi(Delta)((1)O(2)): 0.41-0.58). Furthermore, it has been shown that glucoconjugated photosensitizers could undergo associations with the methyl-beta-cyclodextrin (Me-beta-CD) which exhibit high triplet lifetimes and singlet oxygen yields ranging from 0.27 to 0.48.

The use of 5-aminolevulinic acid (5-ALA) ester derivatives as precursors of endogenous protoporphyrin IX (PpIX) has been proposed as a good strategy for improved drug diffusion across biological membranes. In the present work, the 5-ALA ester derivatives hexyl-ALA (h-ALA), octyl-ALA (o-ALA), and decyl-ALA (d-ALA) were synthesized, and their efficacy to induce endogenous PpIX was explored in a murine melanoma cell line (B-16) as compared with that of 5-ALA. The maximum level of PpIX induced in cells treated with 5-ALA, h-ALA, o-ALA, and d-ALA was reached at optimal concentrations of 0.3, 0.075, 0.1, and 0.075 mM, respectively. The derivatives h-ALA and o-ALA appear as the most efficient PpIX precursors in this cell line, since a higher or similar PpIX production could be achieved with a fourfold and threefold lower dose of these precursors compared with 5-ALA. The phototoxicity effect of h-ALA and o-ALA ester derivatives showed the same phototoxicity behavior detected for 5-ALA but at much lower drug doses. Our study suggests that h-ALA and o-ALA esters improve intracellular PpIX formation in B-16 cells at reduced concentrations. This should enable clinical applications at lower precursor doses with reduced effective costs.

Asymmetrical glycoconjugated tetrapyrrolic macrocycles are under study as efficient sensitizers for photodynamic therapy (PDT). In this context, tri( meta - O -β-glucopyranosyloxyphenyl)chlorin [TPC( m - O -Glu) 3 ] 2a / 3a was found to be four times more photoactive in vitro than Foscan ® . In a further study of this interesting glycoconjugate, its metabolism by cellular glycosidases in HT29 cells has to be explored. Cellular extracts of HT29 cells incubated with TPC( m - O -Glu) 3 (24 h, 6 μM) were analyzed by MALDI-TOF mass spectrometry and high performance liquid chromatography (HPLC). In MALDI-TOF mass spectra, the presence of compounds distinct from TPC( m - O -Glu) 3 ( m / z 1151) were observed at m / z 989, 827 and 665 corresponding to the loss of one, two or three glucose units (162 u) and were be ascribed to TPC( m -OH)( m - O -Glu) 2 2 / 3b , b ′, b ″, TPC( m -OH) 2 ( m - O -Glu) 2 / 3c , c ′, c ″ and TPC( m -OH) 3 isomers 2d / 3d , respectively. The porphyrins resulting from chlorin oxidation TPP( m - O -Glu) 3 4a , TPP( m -OH)( m - O -Glu) 2 4b , b ″, TPP( m -OH) 2 ( m - O -Glu) 4c , c ″ and TPP( m -OH) 3 4d were also observed. The HPLC profile ( λ anal. =420 nm) showed eight peaks consistent with mass spectra. The kinetics of deglucosylation was studied from HPLC profiles between 1 and 48 h incubation. The concentration of triglucoconjugated and diglucoconjugated molecules was maximum around 3 and 8 h incubation, respectively, whereas, totally deglucosylated species appeared only after incubation for more than 10 h. The fully deglycosylated porphyrin TPP( m -OH) 3 is the final metabolite, being observed at a concentration 15 times higher than that of the remaining TPC( m - O -Glu) 3 2a / 3a . Compared to the photobiological activity of the parent molecule [TPC( m - O -Glu) 3 ], a three times higher TPP( m -OH) 3 concentration was necessary to observe a similar in vitro photoactivity.

meta-Tetra(hydroxyphenyl)chlorin (mTHPC), a second generation photosensitizer used in photodynamic therapy (PDT), was incorporated into long circulating carriers with the aim of improving the tumor selectivity by limiting the reticuloendothelial system (RES) uptake. Biodistribution of mTHPC (0.06 mg kg−1) was studied directly in nude mice bearing HT29 human tumor by optical fiber fluorimetry and tissue drug contents were determined by HPLC after extraction. The drug was incorporated in the oily core of nanocapsules surrounded by poly(D,L lactic acid) (PLA NCs), PLA grafted with polyethylene glycol (PLA-PEG) or PLA coated with poloxamer 188 (polox PLA). Compared to PLA NCs, incorporation of mTHPC in surface-modified nanocapsules resulted in strong modifications of the drug biodistribution and tumoral retention with a three-fold increase of drug level as early as 24 h post-administration. A reduced liver uptake was observed at early times post-administration indicating that surface-modified NCs are effective in limiting the RES uptake and could be potential carriers to enhance the therapeutic ratio of lipophilic photosensitizers. Furthermore, in situ fluorescence measurements and concentration data were found in broad agreement showing that optical fiber fluorimetry is a very sensitive method that can be used to follow the biodistribution of fluorescent drugs in real-time.

Preliminary results of clinical experiments using UV induced autofluorescence spectroscopy in 23 patients with Barrett's esophagus are reported in this paper. Excitation wavelengths of 351 nm and 330 nm were used to induce Barrett's mucosa autofluorescence. Autofluorescence acquisition and signal processing were performed using a CP200 Jobin-Yvon system coupled to a flexible three optical fiber sensor. Three distinct emission bands were observed in the measured spectra after normalization according to the backscattered light power. These emissions were attributed to collagen, elastin, NADH and flavin. Fluorescence intensities and ratios between the emission bands were used to discriminate high grade dysplasia and early stage cancer in Barrett's esophagus from normal surrounding tissues. A significant decrease of the overall fluorescence intensity was observed for the Barrett's mucosa compared to the normal esophageal one. Autofluorescence spectral shape was modified. Collagen and elastin contribution was found to decrease going from normal to tumoral tissue.

Purpose: To assess the ability of argon laser-induced autofluorescence spectroscopy (LIAFS) to discriminate normal from tumor human urothelial cells.Materials and Methods: Emission spectra of single living cells excited at 488 nm. have been studied with a confocal microspectrofluorimeter.Results: Cellular autofluorescence appeared as a broad band with a maximum in the same “green” spectral range, 550 to 560 nm., probably corresponding to oxidized flavoprotein emission. However, the maximum autofluorescence intensity of normal urothelial cells was much higher, 10 times (p less than 0.0001) that of any of the tumor cell types tested.Conclusion: These results, suggesting a significantly reduced oxidized flavoprotein concentration in tumor urothelial cells, should prompt us to evaluate argon LIAFS as a potential tool to detect occult urothelial severe dysplasia and carcinoma in situ.

Urothelial carcinoma in situ (CIS) is clearly related to tumor recurrence and subsequent cancer progression1. CIS detection remains a challenge for urologists since this lesion, which is only a few cell layers in thickness, may be asymptomatic and/or not visible under conventional white light cystoscopy.

The dark interaction of 5-methoxypsoralen (5-MOP) and 8-methoxypsoralen (8-MOP) with plasma membranes was studied using human erythrocyte ghosts as a model. In the presence of ghosts, modifications of the fluorescence characteristics of 5-MOP were observed, together with a quenching of the fluorescence of the tryptophan (Trp) residues of membrane proteins (up to 25%). Moreover, the appearance of an induced circular dichroism indicates that 5-MOP is located in a chiral environment. In contrast, only slight effects were observed in the case of 8-MOP. It is concluded that 5-MOP molecules are located partly within chiral protein sites of the membrane in such a way that a Forster energy transfer can occur from the Trp residues to the psoralen molecules.

The determination of the biacetyl concentration in fats can be achieved by measuring the phosphorescence emission of biacetyl at room temperature. The biacetyl phosphorescence can be sensitized using suitable donors by means of a triplet–triplet energy transfer. The spectroscopic characteristics of four newly synthesized coumarin derivatives, which are soluble in non-polar solvents, have been studied. In order to determine whether a triplet–triplet energy transfer is possible, the energy of the lowest triplet state of these derivatives was determined by using phosphorescence spectroscopy. Their ability to sensitize the biacetyl phosphorescence has been investigated and the 6,7-dihydro-3-ethoxycarbonylpsoralen appeared to be the best sensitizer. In this instance, a biacetyl concentration as low as 0.05 ppb (µg kg–1) can be determined in butter samples.

— The flow linear dichroism properties of covalent adducts derived from the photochemical binding of various psoralen derivatives to salmon sperm DNA were investigated. The psoralens studied include bifunctional derivatives (8-methoxypsoralen,5-methoxypsoralen, tetrahydropyrido [3,4: 4‘,5’] psoralen) and monofunctional derivatives (pyrido [3,4-c] psoralen, 7-methylpyrido [3,4-c] psoralen, 3-carbethoxypsoralen). The orientation of the psoralen moieties (furan-side monoadducts) relative to the orientation of the DNA bases was determined. All of the furan-side monoadducts are characterized by a similar orientation, with mean angles between the psoralen moiety and the normals of the planes of the DNA bases ranging between 70° and values close—but not equal—to 90°. The results are consistent with a pseudo-intercalative adduct geometry, most probably involving stacking interactions with the DNA bases.

— Triplet absorption spectra, triplet extinction coefficient and intersystem crossing for 4',5'-monocycloadducts of 3-carbethoxypsoralen (3-CPs) with thymidine (dThd) and uridine (dUrd) in ethanol have been investigated in order to elucidate whether their triplet state properties could be the limitating step for a further photoreaction of 3-CPs monoadducts with DNA nucleosides. The comparison between the triplet characteristics of 4',5'-monoadducts of 3-CPs and those of 8-methoxypsoralen (8-MOP) shows that the quantum yield is much higher in the case of 3-CPs than for 8-MOP. The monofunctionality of 3-CPs cannot therefore be ascribed to the triplet excited states properties of its monoadducts. It is likely that steric hindrance introduced by the bulky carbethoxy group remains a reasonable explanation.

The intracellular pH (pHi) of Candida albicans blastospores harvested from 8 h or 48 h cultures was determined under identical experimental conditions by two different techniques: 31P-NMR and laser microspectrofluorimetry. Time dependence of pHi was monitored by 31P-NMR on the whole cell population. Microspectrofluorimetry, after loading of the cells with SNARF-1, enabled the determination of pHi in isolated cells and its distribution among the cell population. By this method, the vacuolar pH could not be distinguished from the cytoplasmic pH in C. albicans blastospores, but alkalization of pHi was observed at the beginning of germ tubes. The absolute values of pHi determined by 31P-NMR were slightly different from those obtained by laser microspectrofluorimetry. However, the pH distributions in the cell population were converging. For blastospores in exponential phase a gaussian distribution of pHi was observed with both methods, the cells maintained a steady pHi value when the external pH was varied from 5.5 to 8.5. For cells in stationary phase two pools were identified: the combination of the two techniques demonstrated the presence of two different subpopulations. One of these population (with lower pH) was able to commute to the other one with time as shown by 31P-NMR kinetics. This information is reported here for the first time in C. albicans.

The relative affinity of 5-methoxypsoralen (5-MOP) and 8-methoxypsoralen (8-MOP) towards β-cyclodextrin, a good model for the study of lipophilic interactions in biological systems and a potential drug carrier, has been investigated using spectroscopic and chromatographic methods. The fluorescence emission of 5-MOP in aqueous solution containing β-cyclodextrin (10 −2 M) is found to be markedly blue shifted and enhanced by a factor of 6 whereas no significant changes are observed for 8-MOP. The existence of an induced circular dichroism is evidence for the formation of a 1:1 inclusion complex (association constant K = 400 ±1 50 −1 )M.) Moreover, chromatographic results obtained with a β-cyclodextrin linked stationary phase are consistent with our spectroscopic results and might have interesting analytical implications. These results clearly demonstrate that, in contrast to 8-MOP, 5-MOP exhibits a strong affinity for hydrophobic medium. Interesting pharmacological and analytical applications may result from the possible inclusion of psoralen derivatives into β-cyclodextrin.

— 7-Methyl-pyrido[4,3-c]psoralen (2N-MePyPs) has been synthesized in order to investigate the possible effect of the position of the pyridine-nitrogen atom on the photoreactivity towards DNA and the photobiological activity of pyridopsoralens, a new family of psoralen derivatives. In comparison to its isomer, 7-methyl-pyrido[3,4-c]psoralen (MePyPs), 2N-MePyPs shows a 2.5 times lower DNA photobinding capacity. Photobiological experiments with diploid yeast (Saccharomyces cerevisiae) reveal that this compound differs strikingly from its isomer MePyPs. It has only a weak antiproliferative potential and, per unit dose, a lower capacity than MePyPs for the induction of nuclear genotoxic effects. With respect to these latter features, 2N-MePyPs resembles the monofunctional furocoumarin 3-CPs.