A comparison of the apoptotic and cytotoxic effects of hexanedione derivatives on human non-neuronal lines and the neuroblastoma line SH-SY5Y

The effects of the alpha-diketone derivatives 2,3- and 3,4-hexanediones were investigated in three non-neuronal cell lines (MCF7, HepG2 and CaCo-2) as well as in the neuroblastoma line, SH-SY5Y. The MTT reduction assay was employed to determine the necrotic effects of the alpha-diketones and the neurotoxin 2,5-hexanedione over 4, 24 and 48 hr exposures. Flow cytometry was also used to study the effects of the three isomers on the cell cycle of the SH-SY5Y line only. With 2,5-hexanedione, the mean MTT IC50 decreased more than 10-fold from 4 to 48 hr. The toxicities of both alpha-diketones were similar, with a more than 18-fold increase in sensitivity of the SH-SY5Y at 24 hr compared to that of 4 hr. With flow cytometry at 48 hr, SH-SY5Y apoptosis with 2,5-hexanedione rose throughout the concentration range evaluated (0-30 mM) while 2,3- and 3,4-hexanediones showed apoptosis over the concentration range 1-1.6 mM, with 3,4-hexanedione being the more potent compared to the 2,3-isomer. At 1.6 mM nearly all the cells had entered apoptosis in the presence of the 3,4-isomer, (94.9 ± 1.4%) but only 57.5 ±4.1% of the 2,3-isomer-treated cells had reached that stage. The 2,3-and 3,4-isomers in diets alone may not pose a serious threat to human health. Further studies may be necessary to evaluate the effects of other dietary components on their toxicity. These alpha-diketones also display a degree of toxic selectivity towards neuroblastoma cells, which may have therapeutic implications.

An Expansion Formula for Fractional Derivatives and its Application

An expansion formula for fractional derivatives given as in form of a series involving function and moments of its k-th derivative is derived. The convergence of the series is proved and an estimate of the reminder is given. The form of the fractional derivative given here is especially suitable in deriving restrictions, in a form of internal variable theory, following from the second law of thermodynamics, when applied to linear viscoelasticity of fractional derivative type.

Fractional Derivatives and Fractional Powers as Tools in Understanding Wentzell Boundary Value Problems for Pseudo-Differential Operators Generating Markov Processes

Mathematics Subject Classification: 26A33, 31C25, 35S99, 47D07.

On the Equivalence of the Riemann-Liouville and the Caputo Fractional Order Derivatives in Modeling of Linear Viscoelastic Materials

Mathematics Subject Classification: 26A33

On a Differential Equation with Left and Right Fractional Derivatives

Mathematics Subject Classification: 26A33; 70H03, 70H25, 70S05; 49S05

On Arrangements of Real Roots of a Real Polynomial and Its Derivatives

2000 Mathematics Subject Classification: 12D10.

On Root Arrangements of Polynomial-Like Functions and their Derivatives

2000 Mathematics Subject Classification: 12D10.

Large and Moderate Deviations Principles for Recursive Kernel Estimator of a Multivariate Density and its Partial Derivatives

2000 Mathematics Subject Classification: 62G07, 60F10.

Calculus of Variations with Classical and Fractional Derivatives

MSC 2010: 49K05, 26A33

Válság és hitelderivatívák. A szintetikus fedezett adósságkötelezettségek (CDO-k) árazása és kockázataik (Crisis and loan derivatives. The pricing and risks of synthetic collateralized debt obligations)

A dolgozat első részében röviden áttekintjük a 2007-ben kezdődött pénzügyi válság lefolyását és a válsághoz vezető okokat. A bemutatás során igyekszünk végig a mögöttes folyamatokra és azok mozgatórugóira koncentrálni, ezzel megragadva a válság egyfajta "elméletét". A bemutatásból láthatóvá válik a hitelderivatívák kiemelt szerepe a válság során. A dolgozat második részében az egyik legnépszerűbb hitelderivatív termék, a szintetikus fedezett adósságkötelezettségek (CDO-k) matematikai modellezését és annak problémáit mutatjuk be. Sokak szerint ezek a matematikai modellek okozták - vagy legalábbis felerősítették - a válságot. Az elemzés során megmutatjuk, hogy nemcsak a modellezési eszközök nem voltak megfelelők, hanem az árazás elve sem állta meg a helyét a kockázatsemleges árazási keretben. Ez az eredmény élesen rámutat a mögöttes elméletek válságára. / === / The first part of the paper examines briefly the financial crisis of 2007 and its causes, focusing on its driving processes and key motifs. This shows clearly the importance and centrality of credit derivatives in the crisis. The second part presents a mathematical modelling of one of the most popular credit derivative products: synthetic collateralized debt obligations, along with the drawbacks and problems of the modelling process. It is widely claimed that these products caused or at least precipitated the crises. The authors show not only that the modelling tools were inappropriate, but that the principle for pricing did not match adequately the risk-neutral valuation framework.

Derivatív pénzügyi termékek árdinamikája és az új típusú kamatlábmodellek (Interest rate models and the price processes of financial derivatives)

Ennek a cikknek az a célja, hogy áttekintést adjon annak a folyamatnak néhány főbb állomásáról, amit Black, Scholes és Merton opcióárazásról írt cikkei indítottak el a 70-es évek elején, és ami egyszerre forradalmasította a fejlett nyugati pénzügyi piacokat és a pénzügyi elméletet. / === / This review article compares the development of financial theory within and outside Hungary in the last three decades starting with the Black-Scholes revolution. Problems like the term structure of interest rate volatilities which is in the focus of many research internationally has not received the proper attention among the Hungarian economists. The article gives an overview of no-arbitrage pricing, the partial differential equation approach and the related numerical techniques, like the lattice methods in pricing financial derivatives. The relevant concepts of the martingal approach are overviewed. There is a special focus on the HJM framework of the interest rate development. The idea that the volatility and the correlation can be traded is a new horizon to the Hungarian capital market.

The 4-aza-S-ribosyl-L-homocysteine derivatives and the related gamma-lactam and azahemiacetal analogs: Synthesis, inhibition and quorum sensing activity

Quorum sensing (QS) is a population-dependent signaling process bacteria use to control multiple processes including virulence, critical for establishing infection. There are two major pathways of QS systems. Type 1 is species specific or intra-species communication in which N-acylhomoserine lactones (Gram-negative bacteria) or oligopeptides (Gram-positive bacteria) are employed as signaling molecules (autoinducer one). Type 2 is inter-species communication in which S-4,5-dihydroxy-2,3-pentanedione (DPD) or its borate esters are used as signaling molecules. The DPD is biosynthesized by LuxS enzyme from S-ribosylhomocysteine (SRH). Recent increase in prevalence of bacterial strains resistant to antibiotics emphasizes the need for the development of new generation of antibacterial agents. Interruption of QS by small molecules is one of the viable options as it does not affect bacterial growth but only virulence, leading to less incidence of microbial resistance. Thus, in this work, inhibitors of both N-acylhomoserine lactone (AHL) mediated intra-species and LuxS enzyme, involved in inter-species QS are targeted. The γ-lactam and their reduced cyclic azahemiacetal analogs, bearing the additional alkylthiomethyl substituent, were designed and synthesized targeting AHL mediated QS systems in P. aeruginosa and Vibrio harveyi. The γ-lactams with nonylthio or dodecylthio chains acted as inhibitors of las signaling in P. aeruginosa with moderate potency. The cyclic azahemiacetal with shorter propylthio or hexylthio substituent were found to strongly inhibit both las and rhl signaling in P. aeruginosa at higher concentrations. However, lactam and their azahemiacetal analogs were found to be inactive in V. harveyi QS systems. The 4-aza-S-ribosyl-L-homocysteine (4-aza-SRH) analogs and 2-deoxy-2-substituted-S-ribosyl-L-homocysteine analogs were designed and synthesized targeting Bacillus subtilis LuxS enzyme. The 4-aza-SRH analogs in which oxygen in ribose ring is replaced by nitrogen were further modified at anomeric position to produce pyrrolidine, lactam, nitrone, imine and hemiaminal analogs. Pyrrolidine and lactam analogs which lack anomeric hydroxyl, acted as competitive inhibitors of LuxS enzyme with KI value of 49 and 37 µM respectively. The 2,3-dideoxy lactam analogs were devoid of activity. Such findings attested the significance of hydroxyl groups for LuxS binding and activity. Hemiaminal analog of SRH was found to be a time-dependent inhibitor with IC50 value of 60 µM.

Study of Ammonia Borane and its Derivatives: Influence of Nanoconfinements and Pressures

Recently, ammonia borane has increasingly attracted researchers’ attention because of its merging applications, such as organic synthesis, boron nitride compounds synthesis, and hydrogen storage. This dissertation presents the results from several studies related to ammonia borane. The pressure-induced tetragonal to orthorhombic phase transition in ammonia borane was studied in a diamond anvil cell using in situ Raman spectroscopy. We found a positive Clapeyron-slope for this phase transformation in the experiment, which implies that the phase transition from tetragonal to orthorhombic is exothermic. The result of this study indicates that the rehydrogenation of the high pressure orthorhombic phase is expected to be easier than that of the ambient pressure tetragonal phase due to its lower enthalpy. The high pressure behavior of ammonia borane after thermal decomposition was studied by in situ Raman spectroscopy at high pressures up to 10 GPa. The sample of ammonia borane was first decomposed at ~140 degree Celcius and ~0.7 GPa and then compessed step wise in an isolated sample chamber of a diamond anvil cell for Raman spectroscopy measurement. We did not observe the characteristic shift of Raman mode under high pressure due to dihydrogen bonding, indicating that the dihydrogen bonding disappears in the decomposed ammonia borane. Although no chemical rehydrogenation was detected in this study, the decomposed ammonia borane could store extra hydrogen by physical absorption. The effect of nanoconfinement on ammonia borane at high pressures and different temperatures was studied. Ammonia borane was mixed with a type of mesoporous silica, SBA-15, and restricted within a small space of nanometer scale. The nano-scale ammonia borane was decomposed at ~125 degree Celcius in a diamond anvil cell and rehydrogenated after applying high pressures up to ~13 GPa at room temperature. The successful rehydrogenation of decomposed nano-scale ammonia borane gives guidance to further investigations on hydrogen storage. In addition, the high pressure behavior of lithium amidoborane, one derivative of ammonia borane, was studied at different temperatures. Lithium amidoborane (LAB) was decomposed and recompressed in a diamond anvil cell. After applying high pressures on the decomposed lithium amidoborane, its recovery peaks were discovered by Raman spectroscopy. This result suggests that the decomposition of LAB is reversible at high pressures.

Computer assisted synthesis and in-vitro cytotoxic evaluation of new pyrazole-fused isoquinolinoquinones derivatives as PI3K receptor antagonist with promising antitumoral activity

The importance of pyrazole and isoquinoline-5,8-dione scaffolds in medical chemistry is underlined by the high number of drugs currently on trading that contains these active ingredients. Due to their cytotoxic capability, the interest of medicinal chemists in these heterocyclic rings has grown exponentially especially, for cancer therapy. In this project, the first synthesis of pyrazole-fused isoquinoline-5,8-diones has been developed. 1,3-Dipolar cycloaddition followed by oxidative aromatization, established by our research group, has been employed. Screening of reaction conditions and characterization studies about the regioselectivity have been successfully performed. A remote control of regioselectivity, to achieve the two possible regioisomers has been accomplished. Through Molecular Docking studies, Structure-Activity relationship of differently substituted scaffolds containing our central core proved that a family of PI3K inhibitors have been discovered. Finally, in order to verify the promising antitumor activity, a first test of cell viability in vitro on T98G cell line of a solid brain tumor, the Glioblastoma Multiforme, showed cytotoxic inhibition comparable to currently trade anticancer drugs.

Reactions of nitrilium salts with indole and pyrrole and their derivatives in the synthesis of imines, ketones and secondary amines

I thank SERC for a CASE studentship (to RG. Giles) with the former Fisons Pharmaceuticals division (with Dr. S. C. Eyley) and Dr. B. R. Buckley, of this department, for provided helpful comments on an earlier version of the manuscript.