Antitumor studies. Part 4: Design, synthesis, antitumor activity, and molecular docking study of novel 2-substituted 2-deoxoflavin-5-oxides, 2-deoxoalloxazine-5-oxides, and their 5-deaza analogs

Various novel 10-alkyl-2-deoxo-2-methylthioflavin-5-oxides and their 2-alkylamino derivatives were prepared by facile nitrosative cyclization of 6-(N-alkylanilino)-2-methylthiopyrimidin-4(3H)-ones followed by nucleophilic replacement of the 2-methylthio moiety by different amines, and acidic hydrolysis of the 2-methylthio moiety afforded the corresponding flavin derivatives. 2-Deoxo-2-methylthio-5-deazaalloxazines and 2-deoxo-2-methylthioalloxazine-5-oxides were also prepared by Vilsmeier reaction and by nitrosation of 6-anilino-2-methylthiopyrimidin-4(3H)-ones, respectively. Then, they were subjected to nucleophilic replacement with appropriate amines to produce the corresponding 2-alkylamino derivatives. Regiospecific N-3-alkylation of 2-deoxo-2-methylthioalloxazine-5-oxides was carried out with various alkylating agents in the usual way, The antitumor activities against CCRF-HSB-2 and KB tumor cells have been investigated in vitro, and many compounds showed promising antitumor activities. Furthermore, AutoDock molecular docking into PTK (PDB: 1t46) has been done for lead optimization of the aforementioned compounds as potential PTK inhibitors

Studies on Regioselective Binding Mode of Steroid Molecules in Homology Modeled Cytochrome P450-2C11

In this study, we investigated the regioselective binding mode of steroid molecules and structure requirements for steroid molecules for 16[alpha]-hydroxylation by Cytochrome P450-2C11. Docking study by using the homology Cytochrome P450-2C11 indicated that 16[alpha]-hydroxylation is favored with steroidal molecules possessing the following components, 1) a bent A-B ring configuration (5[beta]-reduced), 2) C-3[alpha]-hydroxyl group, 3) C-17[beta]-acetyl group, and 4) methyl group at both the C-18 and C-19. These respective steroid components requirements such as A-B ring configuration and functional groups at C-3 and C-17 were defined as the inhibitory contribution factor. Overall results by rat CYP2C11 revealed that steroidal structure requirements resulted in causing an effective inhibition of [^3^H]progesterone 16[alpha]-hydroxylation by the adult male rat liver microsome. As far as docking of homology modeled CYP2C11 against investigated steroids is concerned, they are docked at the active site superimposed with flurbiprofen. It was also found that the distance between heme iron and C16[alpha]-H was between 4 to 6 Å and that the related angle was in the range of 180±45°

Photometric and Spectroscopic Analysis of the SX Phe Star BL Cam

In the present paper, we report the photometric and spectroscopic observations obtained by the 1.88 m telescope at the Kottamia astronomical observatory of the pulsating star BL Cam. Fourier analysis of the light curves reveals that the fundamental mode has two harmonics. The O-C method is used to establish the period changes. So far, the analysis has been very successful in mapping the pulsation amplitude of the star across the instability strip. By using the formalism of Eddington and Plakidis (1929), we found significant results and strong indications of the evolutionary period change. A total of 55 new maximum light timings are reported. New values of (1/P) dP/dt are estimated using the O-C diagram based on all newly obtained times of maximum light combined with those taken from the literature, assuming the periods are decreasing and changing smoothly. To compute the effective temperature and surface gravity of the star, we performed model atmosphere analysis on its spectra. The physical parameters of the star are calculated and compared with the evolutionary models

The Mechanism of Monitoring and Tracking of Healthcare Systems

This work concerned with e-healthcare that transmit digital medical data through healthcare system. Online monitoring is concentrated on the process of monitoring and tracking of people at home, car, office, and any other location. e-healthcare deals with patients that they are located far from doctor jurisdiction. Healthcare monitoring including measurements of temperature, blood pressure / pulse monitors and ECG, etc. This works deals with the development of monitoring system via adding intelligent system to distinguish the emergency cases. This work try to keep patient data privacy, reduce attack or penetration of data, reduce processing time and at the same time increasing the efficiency of the overall system. The privacy of patient data is critical so this must maintain the confidentiality of information from intrusion

Hiding data in images using steganography techniques with compression algorithms

Steganography is the science and art of secret communication between two sides that attempt to hide the content of the message. It is the science of embedding information into the cover image without causing a loss in the cover image after embedding.Steganography is the art and technology of writing hidden messages in such a manner that no person, apart from the sender and supposed recipient, suspects the lifestyles of the message. It is gaining huge attention these days as it does now not attract attention to its information's existence. In this paper, a comparison of two different techniques is given. The first technique used Least Significant Bit (LSB) with no encryption and no compression. In the second technique, the secret message is encrypted first then LSB technique is applied. Moreover, Discrete Cosine Transform (DCT) is used to transform the image into the frequency domain. The LSB algorithm is implemented in spatial domain in which the payload bits are inserted into the least significant bits of cover image to develop the stego-image while DCT algorithm is implemented in frequency domain in which the stego-image is transformed from spatial domain to the frequency domain and the payload bits are inserted into the frequency components of the cover image.The performance of these two techniques is evaluated on the basis of the parameters MSE and PSNR

Antitumor studies. Part 1: Design, synthesis, antitumor activity, and AutoDock study of 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides as a new class of antitumor agents

Novel 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides were prepared as a new class of antitumor agents and showed significant antitumor activities against NCI-H 460, HCT 116, A 431, CCRF-HSB-2, and KB cell lines. In vivo investigation, 2-deoxo-10-methyl-2-phenyl-5-deazaflavin exhibited the effective antitumor activity against A 431 human adenocarcinoma cells transplanted subcutaneously into nude mouse. Furthermore, AutoDock study has been done by binding of the flavin analogs into PTK pp60(c-src), where a good correlation between their IC50 and AutoDock binding free energy was exhibited. In particular, 2-deoxo-2-phenylflavin-5-oxides exhibited the highest potential binding affinity within the binding pocket of PTK

Antitumor studies. Part 3: Design, synthesis, antitumor activity, and molecular docking study of novel 2-methylthio-, 2-amino-, and 2-(N-substituted amino)-10-alkyl-2-deoxo-5-deazaflavins

Various novel 10-alkyl-2-deoxo-2-methylthio-5-deazaflavins have been synthesized by reaction of 6-(N-alkylanilino)-2-methylthiopyrimidin-4(3H)-ones with Vilsmeier reagent. The similar 2-(N-substituted amino) derivatives were prepared by nucleophilic replacement reaction of the 2-methylthio moiety by appropriate amines. The 2-oxo derivatives (i.e., 5-deazaflavins) were obtained by acidic hydrolysis of the 2-methylthio derivatives. The antitumor activities against CCRF-HSB-2 and KB cells and the antiviral activities against HSV-1 and HSV-2 have been investigated in vitro, and many compounds showed promising antitumor activities. Furthermore, AutoDock molecular docking into PTK has been done for lead optimization of these compounds as potential PTK inhibitors. Whereas, the designed 2-deoxo-5-deazaflavins connected with amino acids at the 2-position exhibited the good binding affinities into PTK with more hydrogen bonds

Lepton polarization asymmetry and forward backward asymmetry in exclusive B->K_1 tau^(+)tau^(-) decay in universal extra dimension scenario

Decay rate, forward-backward asymmetry and polarization asymmetries of final state leptons in B-> K_{1}tau ^{+}tau ^{-}, where K_{1} is the axial vector meson, are calculated in Standard Model and in the universal extra dimension (UED) model. The sensitivity of the observables on the compactification radius $R$, the only unknown paramter in UED model, is studied. Finally, the helicity fractions of the final state K_{1} are calculated and their dependence on the compactification radius is discussed. This analysis of helicity fraction is briefly extended to B->K^{*}l ^{+}l ^{-}(l =e,mu) and compared with the other approaches exist in the literatureComment: 19 pages, 6 figure

Rare Charm Decays in the Standard Model and Beyond

We perform a comprehensive study of a number of rare charm decays, incorporating the first evaluation of the QCD corrections to the short distance contributions, as well as examining the long range effects. For processes mediated by the $c\to u\ell^+\ell^-$ transitions, we show that sensitivity to short distance physics exists in kinematic regions away from the vector meson resonances that dominate the total rate. In particular, we find that $D\to\pi\ell^+\ell^-$ and $D\to\rho\ell^+\ell^-$ are sensitive to non-universal soft-breaking effects in the Minimal Supersymmetric Standard Model with R-parity conservation. We separately study the sensitivity of these modes to R-parity violating effects and derive new bounds on R-parity violating couplings. We also obtain predictions for these decays within extensions of the Standard Model, including extensions of the Higgs, gauge and fermion sectors, as well as models of dynamical electroweak symmetry breaking.Comment: 45 pages, typos fixed, discussions adde

Synthesis, Docking and Biological Activities of Novel Hybrids Celecoxib and Anthraquinone Analogs as Potent Cytotoxic Agents

Herein, novel hybrid compounds of celecoxib and 2-aminoanthraquinone derivatives have been synthesized using condensation reactions of celecoxib with 2-aminoanthraquinone derivatives or 2-aminoanthraquinon with celecoxib derivatives. Celecoxib was reacted with different acid chlorides, 2-chloroethylisocyanate and bis (2-chloroethyl) amine hydrochloride. These intermediates were then reacted with 2-aminoanthraquinone. Also the same different acid chlorides and 2-chloroethylisocyanate were reacted with 2-aminoanthraquinone and the resulting intermediates were reacted with celecoxib to give isomers for the previous compounds. The antitumor activities against hepatic carcinoma tumor cell line (HEPG2) have been investigated in vitro, and all these compounds showed promising activities, especially compound 3c, 7, and 12. Flexible docking studies involving AutoDock 4.2 was investigated to identify the potential binding affinities and the mode of interaction of the hybrid compounds into two protein tyrosine kinases namely, SRC (Pp60v-src) and platelet-derived growth factor receptor, PDGFR (c-Kit). The compounds in this study have a preferential affinity for the c-Kit PDGFR PTK over the non-receptor tyrosine kinase SRC (Pp60v-src)