Potansiyel antibiyotik ve antitümör özelliklere sahip yeni ferrosen türevlerinin tasarım ve sentezi

TÜBİTAK TBAG01.10.2008Ferrosen ve ferrosenyum tuzlarının son yapılan çalışmalarda antitümör aktivite göstermesinden sonra yapılarında ferrosen grubu ihtiva eden biyoaktif yapılar büyük önem kazanmıştır çünkü ferrosen grubu bu bileşiklerin sahip oldukları antitümör ve antibiyotik etkileri dahada artırmaktadır. Dolayısıyla daha etkili antitümör maddelerinin bulunması ve geliştirilmesi kanser gibi hastalıkların tedavisinde yeni umutlar olabilir. Organik ve organometalik bileşiklerin biyolojik aktiviteleri hakkında bazı tahminler yapılabilmekle beraber aktivitelerin kesin olarak belirlenmesi ancak biyolojik aktivite testleri ile mümkündür. Bu da genellikle bu bileşiklerin önce eldesini yani laboratuvarda sentezini gerektirmektedir. Bir ferrosenil grubunun antitümör ve antibiyotik gibi önemli biyolojik aktivitelere sahip alkilidensiklopentendion (1), siklopentenon (2), sikloheptadienon (3) ve pirazol (4) yapılarına direk bağlı olduğu bu tür türevler literatürde hemen hemen bilinmemekte ve bunların sentezine yönelik herhangi bir çalışmada yoktur. Bu projede yeni ve uygulanabilir yöntemler geliştirilerek yapıları aşağıda gösterilen literatürde bilinmeyen bu yeni ferrosenii türevlerinin sentezi gerçekleştirilmiştir. Ferrosenil grubunun bu maddelerin sahip oldukları biyolojik aktiviteyi dahada artırması beklenmektedir. Sentezlenen bu bileşiklerden bir veya bir kaçının istenilen düzeyde biyolojik aktivite göstermesi halinde bu bileşikler kanser gibi hastalıkların tedavisinde umut verici yeni ilaç maddeleri olabileceklerdir.After ferrocene and ferrocenium salts have shown antitumor activities in recent studies, biologically active compounds containing a ferrocene moiety have gained more importance since the ferrocene group increases their antitumor and antibiotic activities more and more. Development of new potential antitumor compounds is likely to provide new promising drug substances for curing the cancer type diseases. Although the biological activities of organic and organometallic compounds/complexes can be predicted to some extent, the certain activities can be determined only by their biological activity tests, which would require first the laboratory synthesis of such compounds/complexes. The examples of ferrocenyl-substituted alkylidenecyclopentenediones (1), cyclopentenones (2), cycloheptadienones (3) and pyrazoles (4), as well as general methods for their syntheses, are almost unknown, but these compounds should be medicinally very important compounds. In this project, the synthesis of these new compounds, which are unknown in literature, was achieved by developing new and applicable methods. It is expected that ferrocenyl moiety will increase their current biological activity more and more. If one or few of them shows the expected biological activity, then such compounds can be promising drug candidates to cure the cancer type diseases

Parametrik olmayan regresyon modeline hesaplamalı bir yaklaşım :

Bootstrapping is a resampling technique which treats the original data set as a population and draws samples from it with replacement. This technique is widely used, especially, in mathematically intractable problems. In this study, it is used to obtain the empirical distributions of the parameters to determine whether they are statistically significant or not in a special case of nonparametric regression, Conic Multivariate Adaptive Regression Splines (CMARS). Here, the CMARS method, which uses conic quadratic optimization, is a modified version of a well-known nonparametric regression model, Multivariate Adaptive Regression Splines (MARS). Although performing better with respect to several criteria, the CMARS model is more complex than that of MARS. To overcome this problem, and to improve the CMARS performance further, three different bootstrapping regression methods, namely, Random-X, Fixed-X and Wild Bootstrap are applied on four data sets with different size and scale. Then, the performances of the models are compared using various criteria including accuracy, precision, complexity, stability, robustness and efficiency. Random-X yields more precise, accurate and less complex models particularly for medium size and medium scale data even though it is the least efficient method.M.S. - Master of Scienc

Zaman serisinde kırılma noktalarını bulmak için hesaplamalı istatistik yaklaşımı.

Detection of possible inhomogeneity within a series is an important problem in time series data. There are many sources from which inhomogeneity can be originated such as mean shift, variance and trend change, gradual change, or sudden decrease or increase in time series. Since time series has many application areas, the detection of changepoints should be investigated before conducting any analysis. Available methods have certain drawbacks that may lead to unreliable inferences. These include the need of independent and identically distributed variables or normality assumption of observations whose validation may not be possible for dependent data or need of highly correlated reference series. In this thesis, a computational approach is proposed to obtain an absolute test to detect whether data is homogeneous or not. For this purpose, likelihood ratio test for mean shift for AR(1) models is considered and then, moving block bootstrap is used to detect the breakpoints especially close to the beginning or end of the series. In order to derive the related test statistic, exact likelihood is used and the critical values of the test statistic is obtained by a simulation study for different sample sizes and an appropriate length of blocks is suggested to detect changepoints. Then, the performance of the proposed method is compared with the best performing tests in the literature. The comparison study and real life applications reveal that the proposed method performs better than the methods in the literature.Ph.D. - Doctoral Progra

4-iyotpirazol türevlerinin sentezi.

Pyrazoles have been studied for over a century as an important class of heterocyclic compounds and continue to attract considerable interest due to the broad range of biological activities they possess. The electrophilic cyclization of the acetylenic hydrazones initiated by molecular iodine could provide new ways of synthesizing biologically active 4-iodopyrazole derivatives, which are important precursors for the synthesis of highly substituted pyrazole derivatives. For this reason, we investigated the synthesis of 4-iodopyrazole derivatives, such as 1-aryl- 5-alkyl/aryl-4-iodopyrazoles, starting from phenylhydrazine and , -acetylenic aldehyde derivatives. Initially, , -acetylenic aldehydes were synthesized by formylation reaction of corresponding alkynes with DMF. Then, hydrazone derivatives of these aldehydes were prepared by heating them with phenylhydrazine in a neat manner at 55 °C for 5 h. Finally, acetylenic phenyl hydrazone derivatives were subjected to electrophilic cyclization by treating with excess molecular iodine at 80 °C for 3 h. Although electrophilic cyclization is commonly used in organic chemistry, it has not been employed for the cyclization of acetylenic phenyl hydrazones to pyrazole derivatives. Under optimized conditions, these reactions afforded 1-aryl-5-alkyl/aryl-4-iodopyrazole derivatives in moderate to good yields as the single or the major product of the reactions. In some cases, 1-aryl-5-alkyl/arylpyrazole derivatives resulted from these reactions as minor products. In conclusion, 4-iodopyrazole derivatives were synthesized for the first time directly from acyclic starting materials, , -acetylenic phenylhydrazones and iodine, via electrophilic cyclization.M.S. - Master of Scienc

Meteorolojik Verilerin Hesaplamalı İstatistiksel Yöntemlerle Türdeşlik Analizi

Türdeşlik analizi, zaman serisi verisi için önemli bir araştırma konusudur. Ortalamada değişim, varyantsa değişim, eğilim oluşumu, ani ya da kademeli artış veya azalma gibi birçok durum türdeşliği bozan sebeplerdir. Türdeşlik literatüründe kullanılan yöntemlerin birçoğunda güvenli olmayan sonuçlara yol açabilecek varsayımlar ya da yaklaşımlar bulunmaktadır. Bunlardan bazıları; bağımsızlık ve özdeşlik ya da normallik varsayımı gibi zaman serisi için gerçekçi olmayan durumlardır. Bu projede, bir hesaplamalı istatistik yaklaşımı olan koruyan halka yönteminin kullanımı ile literatürdeki yöntemlerin geliştirilmesi ya da yeni bir yöntem oluşturularak verinin türdeşlik analizinin yapılması planlanmaktadır

Detection performance of likelihood ratio test for change points based on bootstrap for AR 1 models

he detection of change-points in time series is an important issue especially in economics, finance, meteorology and energy. Change in mean, change in variance or any sudden increase or decrease in the series can cause breakpoints. In AR(1) models, the likelihood ratio test is conducted to test for a single breakpoint. However, if the sample size is small or the location of the breakpoint is close to the end or the beginning of the series, the detection performance becomes worse. In order to increase the correct detection percentage of the likelihood ratio test in these cases, a bootstrap method for dependent data is applied and its performance is investigated when the change is only in the mean under several breakpoint scenarios. The test is applied to simulated data and the results are compared with the results obtained from tests in the literature