Hit to Leads with Cytotoxic Effect in Leukemic Cells: Total Synthesis Intermediates as a Molecule Treasure Chest

A previously designed and developed 12-step total synthesis that includes [1,1′-biphenyl]-2-amine and carbazole intermediates and that ultimately produces the carbazole alkaloid carbazomycin G was exploited as a screening compound library with the goal of identifying potential lead compound(s) with cytotoxic effect. These compounds were investigated by using in-vitro tests involving the two human cell lines HL-60 and MOLM-13, which both model acute myeloid leukaemia (AML). The in-vitro biological test results were used together with the molecular structures of the various intermediates in a concise SAR analysis. Several of the intermediates revealed cytotoxicity (IC₅₀<10⁻⁴ M), although the final natural product carbazomycin G did not reveal cytotoxicity versus the two said human cell lines.     

Appraisal of Agriglass in Promoting Maize Production Under Abiotic Stress Conditions

An agriglass composition containing different oxides acts as a slow release for macro and micro nutrients and was chosen to improve maize yield under most important abiotic stresses which affecting agriculture development; salinity and drought. A field experiment was performed in salt affected soil (EC =?7.5 dSm^??1) by using different water deficit rates (I1 = 100, I2 = 85 and I3 = 70% of maize water requirements). Irrigation levels were located in main plots. Every main-plot divided into six sub-plots contained glassy fertilizer treatments [F1 = 55 kg fed^?1 with 1/2 mm diameter of agriglass (fed. =?4200 m²), F2 = 55 kg fed^?1 with 1 mm diameter, F3 = 80 kg fed^?1 with 1/2 mm diameter, F4 = 80 kg fed^?1 with 1 mm diameter, F5 = Recommendations of Ministry of Agriculture and F6 = control]. The experimental results demonstrated that, ears, straw, grains and biological yields increased with increasing both water and agriglass rates. Application of agriglass as a slow release fertilizer improved yield more than mineral fertilizer. Some growth parameters, water use efficiency (IWUE), macronutrients concentration and their relations were included. Other studies on residual effect of agriglass and the annual application rates to withstand salinity and drought stress by strategic crops are required.     

Radiolabeling,Preparation, and Bioevaluation of 99mTc-Azathioprine as a Potential Targeting Agent for Solid Tumor Imaging

Radiochemistry - Azathioprine, an antitumor agent, was labeled with 99mTc using stannous chloride dihydrate as a reducing agent. Factors such as the amounts of the reducing agent and substrate, pH,...     

Assessment of Dam Overtopping Reliability using SUFI Based Overtopping Threshold Curve

Estimation of earth-fill dam height and dimension of spillway are strongly depend on accurate evaluation of dam overtopping reliability. Ideally, whole random and effective variables on overtopping should be considered for dam overtopping reliability assessment. However, taking into account all affecting random variables as well as overtopping reliability assessment using algorithms such as Monte Carlo (MC) could be excessively time consuming and impossible in some cases. In this study, new approach has been introduced as conditional reliability method and it has been tried to reduce the simulations time significantly by using combination of rainfall threshold theory, SUFI (Sequential Uncertainty Fitting) and MC methods. According two defined indexes, the obtain results shown, the relative error of new approach in computation of Jamishan dam overtopping reliability is less than 0.23%. Also, time saving in new method against to regular MC method is more than 87%. So, the new introduced method has more efficiency with acceptable accuracy for assessment of dam overtopping reliability. In addition, among hydrological and hydraulic uncertainties, hydrological uncertainties have more effect on overtopping reliability.     

Reexamination of the Ergothioneine Biosynthetic Methyltransferase EgtD from Mycobacterium tuberculosis as a Protein Kinase Substrate

Ergothioneine has emerged as a crucial cytoprotectant in the pathogenic lifestyle of Mycobacterium tuberculosis. Production of this antioxidant from primary metabolites may be regulated by phosphorylation of Thr213 in the active site of the methyltransferase EgtD. The structure of mycobacterial EgtD suggests that this post-translational modification would require a large-scale change in conformation to make the active-site residue accessible to a protein kinase. In this report, we show that, under in vitro conditions, EgtD is not a substrate of protein kinase PknD.     

Proton-Detected Solid-State NMR of the Cell-Free Synthesized α-Helical Transmembrane Protein NS4B from Hepatitis C Virus

Proton-detected 100 kHz magic-angle-spinning (MAS) solid-state NMR is an emerging analysis method for proteins with only hundreds of microgram quantities, and thus allows structural investigation of eukaryotic membrane proteins. This is the case for the cell-free synthesized hepatitis C virus (HCV) nonstructural membrane protein 4B (NS4B). We demonstrate NS4B sample optimization using fast reconstitution schemes that enable lipid-environment screening directly by NMR. 2D spectra and relaxation properties guide the choice of the best sample preparation to record 2D ¹H-detected ¹H,¹⁵N and 3D ¹H,¹³C,¹⁵N correlation experiments with linewidths and sensitivity suitable to initiate sequential assignments. Amino-acid-selectively labeled NS4B can be readily obtained using cell-free synthesis, opening the door to combinatorial labeling approaches which should enable structural studies.