Weak Interactions of the Isomers of Phototrexate and Two Cavitand Derivatives

The interactions of two conformers of newly synthesized photoswitchable azobenzene analogue of methotrexate, called Phototrexate, with two cavitand derivatives, have been investigated in dimethyl sulfoxide medium. Photoluminescence methods have been applied to determine the complex stabilities and the related enthalpy and entropy changes associated to the complex formation around room temperature. Results show opposite temperature dependence of complex stabilities. The structure of the upper rims of the host molecules and the reordered solvent structure were identified as the background of the opposite tendencies of temperature dependence at molecular level. These results can support the therapeutic application of the photoswitchable phototrexate, because the formation of inclusion complexes is a promising method to regulate the pharmacokinetics of drug molecules

Influence of Aliphatic Chain Length on Structural, Thermal and Electrochemical Properties of n-alkylene Benzyl Alcohols: A Study of the Odd–Even Effect

The century-old, well-known odd–even effect phenomenon is still a very attractive and intriguing topic in supramolecular and nano-scale organic chemistry. As a part of our continuous efforts in the study of supramolecular chemistry, we have prepared three novel aromatic alcohols (1,2- bis[2-(hydroxymethyl)phenoxy]butylene (Do4OH), 1,2-bis[2-(hydroxymethyl)phenoxy]pentylene (Do5OH) and 1,2-bis[2-(hydroxymethyl)phenoxy]hexylene (Do6OH)) and determined their crystal and molecular structures by single-crystal X-ray diffraction. In all compounds, two benzyl alcohol groups are linked by an aliphatic chain of different lengths (CH2)n; n = 4, 5 and 6. The major differences in the molecular structures were found in the overall planarity of the molecules and the conformation of the aliphatic chain. Molecules with an even number of CH2 groups tend to be planar with an all-trans conformation of the aliphatic chain, while the odd-numbered molecule is non-planar, with partial gauche conformation. A direct consequence of these structural differences is visible in the melting points—odd-numbered compounds of a particular series display systematically lower melting points. Crystal and molecular structures were additionally studied by the theoretical calculations and the melting points were correlated with packing density and the number of CH2 groups. The results have shown that the generally accepted rule, higher density = higher stability = higher melting point, could not be applied to these compounds. It was found that the denser packaging causes an increase in the percentage of repulsive H· · · H interactions, thereby reducing the stability of the crystal, and consequently, the melting points. Another interesting consequence of different molecular structures is their electrochemical and antioxidative properties—a non-planar structure displays the highest oxidation peak of hydroxyl groups and moderate antioxidant activit

Az indvidualizált farmakoterápia lehetőségének kidolgozása - súlyos bőrgyógyászati mellékhatásokkal is járó adverz gyógyszerreakciók farmakogenomikai és etiológiai vizsgálata, genetikai megelőzése, preventív rendszerek, tesztek fejlesztése = Working towards the realization of personalized medicine - pahrmacogenomic and etiological study of adverse drug reactions with severe cutan involvement, developing preventive systems and assays

Pharmacogenomika: 80 lamotrigint vagy carbamazepint szedő beteg- súlyos cután gyógyszermellékhatással vagy a nélkül adatait és DNS-ét archiváltuk. A DNS mintákat CYP2D6 és CYP2C19 polymorphismusra Amplichip CYP450 IVD kittel Affymetrix Gene Chip Fluidics Station 450-en és/vagy Affymetrix Drug Metabolizing Enzymes and Transporters (DMET+) rendszerben vizsgáltuk. 4 technikai probléma- prolongált vizsgálat: 1, Az első mérések elavult software-t jeleztek, cseréltük 2. Ez új 7G reading chip rendszert igényelt. A 4 állomásból 3 működik 3, A két Roche teszt-chip lejárt kóddal érkezett 4, Előzetes génvizsgálatokat kezdtük az Affymetrix Genotyping Console software-rel, DMET chipeken, de a releváns eredmények PCR re-tesztelése most zajlik. További vizsgálatok Állati eredetű anabolikus steroidok és fokozott aminosav bevitele volt a kiváltó faktor eosinophil fasciitises testépítő betegünkben,akiben a készítmények alkalmazását követően új, állati eredetű mycoplasma arginini fertőzést igazoltunk. Súlyos gyógyszermellékhatásban szenvedő betegeinket teszteltünk társuló mycoplasma infekciókat PCR-rel és szerológiai módszerekkel. Bevezettük az epicutan gyógyszertesztelést tünetmentes betegeinkben. Atomerőműben szűrtünk bőrdaganatokat- szabadidős UV expozíció hatását igazoltuk- (fényérzékenyítő gyógyszereket nem szedtek). Két magyar összefoglaló tanulmány: 1, Toxicodermákban végzett LTT tesztek eredményéről 2, Erythema multiformében a gyógyszermellékhatásgyakoriságáról. | Pharmacogenomics: data and DNA from 80 patients under lamotrigine or carbamazepine therapy with or without severe cutaneous adverse effects were collected. DNAs were analyzed for CYP2D6 and CYP2C19 polymorphisms by Amplichip CYP450 IVD kit on an Affymetrix Gene Chip Fluidics Station 450 and by Affymetrix Drug Metabolizing Enzymes and Transporters (DMET + Solution) chip. 4 problems - study prolongation. 1, Uncertain data indicated an old software system, the change needed new 7G reading chips in our Affymetrix Station. 2,Still, one out of 4 stations is not working currently 3, Two Roche test chips arrived by expired codes 4, Preliminary genetic studies were also performed by an Affymetrix Genotyping Console software on a DMET chip and relevant genes and polymorphisms are currently under PCR re-testing. Further studies In a patient with eosinophil fasciitis induced by anabolic steroid and aminoacid intake from uncontrolled animal sources we identified a new animal mycoplasma arginini infection. In patients severe drug adverse reactions associated mycoplasma infections were studied by PCR and immunology. We introduced the patch testing for drug sensitivity. In a Hungarian nuclear power plant screened for cutaneous malignancies the role of outdoor UV was identified - without drug induced photosensitivity. Hungarian papers on lymphocyte transformation drug testing and erythema multiforme also related to drug sensitivity were published

Comparative EPR Study on the Scavenging Effect of Methotrexate with the Isomers of Its Photoswitchable Derivative

The scavenging effect of the antimetabolite dihydrofolate reductase inhibitor methotrexate (MTX) and the isomers of its photoswitchable derivate, cis- and trans-phototrexate (PHX), have been compared by ESR spectroscopy, with the application of a cyclic hydroxylamine spin probe. The results showed the most pronounced scavenging effect in the presence of trans-phototrexate (trans-PHX). At a low concentration (100 µM) cis-PHX also showed a greater scavenging effect than the parent molecule MTX. Direct antioxidant properties of the investigated molecules were measured by ABTS scavenging assay, which showed no significant difference between trans-PHX and cis-PHX, but both of the isomers of PHX showed a higher antioxidant capacity than MTX. These findings imply that trans-PHX may have more pronounced anti-inflammatory and tissue-protective effects than MTX, despite the lack of its cytotoxic, antineoplastic effect

Weak Interaction of the Antimetabolite Drug Methotrexate with a Cavitand Derivative

Formation of inclusion complexes involving a cavitand derivative (as host) and an antimetabolite drug, methotrexate (as guest) was investigated by photoluminescence measurements in dimethyl sulfoxide solvent. Molecular modeling performed in gas phase reflects that, due to the structural reasons, the cavitand can include the methotrexate in two forms: either by its opened structure with free androsta-4-en-3-one-17α-ethinyl arms or by the closed formwhen all the androsta-4-en-3-one-17α-ethinyl arms play role in the complex formation. Experiments reflect enthalpy driven complex formation in higher temperature range while at lower temperature the complexes are stabilized by the entropy gain

Diagnostic relevance of urinary steroid profiles on ovarian granulosa cell tumors: two case reports

Abstract Background Granulosa cell tumor of the ovary is the most frequent sex cord stromal tumor and represents 2 to 5% of all primary ovarian cancers. Ovarian granulosa cell tumor is a malignant tumor with slow progression and in some cases this tumor is hormonally active. The recurrence of granulosa cell tumor often happens after 5 years. Case presentation We describe two cases of postmenopausal women with adult-type granulosa cell tumors of the ovary. Patient 1 is a 49-year-old European woman with a recurrent tumor; patient 2 is a 55-year-old European woman without recurrence of tumor. Urinary steroid profiles of patient 1 were monitored during a 5-year period starting from before an operation (13 samples). In patient 2, the urinary steroid profiles were monitored during a 3-year period starting from after an operation (six samples). The 24-hour urinary samples were examined and the urinary concentration of 20 androgen, progesterone, and corticoid metabolites was quantitatively determined by gas chromatography-mass spectrometry with selected ion-monitoring mode. Conclusions Based on these cases a correlation could be observed between increased levels of the urinary steroids and the recurrence of ovarian granulosa cell tumor; therefore, we concluded that a urinary steroid profile could be a more effective method to follow-up such patients compared to the traditional serum hormones determinations supplemented with conventional tumor markers