Design,synthesis and biological evaluation of spiropyrimidinetriones oxazolidinone derivatives as antibacterial agents

Gram-positive bacteria are among the most common human pathogens associated with clinical infections which range from mild skin infections to sepsis. Resistance towards existing class of drugs by Gram-positive bacteria including methicillin resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE) and vancomycin resistant enterococci (VRE) is a growing concern. There is an urgent need to discover new antibiotics which are active against resistant strains of Gram positive bacteria. We report herein a novel class of spiropyrimidinetrione oxazolidinone derivatives as novel antibacterial agents. Key step towards the synthesis of title compounds involved the use of tert-amino reaction with [1,5]-hydride shift leading to the new CC bond formation. Compound 30n has demonstrated potent antibacterial activity against a panel of Gram-positive microbial strains including MRSA, MRSE, and LNZ and vancomycin resistant strains of E. faecalis. Further, molecular docking studies suggest that 30n has binding mode similar to that of LNZ in 50S RNA ribosome.     

Exploring biological processes involved in embryonic stem cell differentiation by analyzing proteomic data

Since, proteins carry out many functional roles in a cell with different concentrations, proteomics is likely a more appropriate approach to explain biological processes and cellular events than mRNA studies. Although, gene ontology provides a systematic and organized vocabulary of biological terms for proteins, we need more details to decide about the correct duty and annotation of proteins in a specific condition. One can assume that a change of protein concentration is related to a biological process of that protein with negligible error. Therefore, we can obtain more information about the function of proteins by studying these profiles. In this study, we used time-course proteomic data of a twenty day differentiation study of embryonic stem cells (ESCs) differentiating to embryoid bodies (EBs). Hierarchical clustering was used to cluster time-series concentration profile of proteins. Our results demonstrate that there are eleven active processes with distinct concentration profiles in this initial differentiation. According to the concentration profiles of proteins, we suggest new change points (or equivalently, new stages) in the course of embryonic differentiation.     

Artificial neural networking to estimate the leaf area for invasive plant Wedelia trilobata

Leaf area are very important parameter for the understanding of growth and physiological responses of invasive plant species under different environmental factors. This study was conducted to build non-destructive leaf area model of Wedelia trilobata that were grown in greenhouse. Regression analysis and artificial neural network (ANN) approaches were used for the development of leaf area model with the help of leaf length and width of 262 plants samples. In selection of best method under both techniques, the lower value of mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE) and higher value of R² were considered. According to the results it was found that ANN have higher value of (R² = 0.96) and lower value of error (MAE = 0.023, RMSE = 0.379, MAPE = 0.001) than regression analysis (R² = 0.94, MAE = 0.111, RMSE = 1.798, MAPE = 0.0005). It was concluded that error between predicted and actual value was less under ANN. Therefore, ANN model approach can be used as an alternating method for the estimation of leaf area. Through estimation of leaf area, invasive plant growth can predict under different environment conditions.     

MicroRNAs and response to therapy in leukemia

A variety of epigenetic factors involved in leukemia pathogenesis. Among various epigenetic factors, microRNAs (miRNAs) have emerged as important players, which affect a sequence of cellular and molecular signaling pathways. Leukemia is known as progressive cancer, which is related to many health problems in the world. It has been shown that the destruction of the blood-forming organs could lead to abnormal effects on the proliferation and development of leukocytes and their precursors. Despite many attempts for approved effective and powerful therapies for patients with leukemia, finding and developing new therapeutic approaches are required. One of the important aspects of leukemia therapy, identification of underlying cellular and molecular mechanisms involved in the pathogenesis of leukemia. Several miRNAs (ie, miR-103, miR-101, mit-7, let-7i, miR-424, miR-27a, and miR-29c) and play major roles in response to therapy in patients with leukemia. miRNAs exert their effects by targeting a variety of targets, which are associated with response to therapy in patients with leukemia. It seems that more understanding about the roles of miRNAs in response to therapy in patients with leukemia could contribute to better treatment of patients with leukemia. Here, for the first time, we summarized various miRNAs, which are involved in response to therapy in the treatment patients with leukemia.     

Rapid in vitro multiplication and ex vitro establishment of Caribbean copper plant (Euphorbia cotinifolia L.): an important medicinal shrub

An efficient micropropagation protocol was developed for E. cotinifolia by utilizing mature nodal segments for axillary shoot proliferation. The nodal explants from a 2-year-old plant were cultured on Murashige and Skoog (MS) medium supplemented with different concentrations (0.5, 2.5, 5.0, 7.5 and 10.0 μM) of 6-benzyladenine (BA), Kinetin and 2-isopentenyl adenine singly as well as in combination with α-naphthalene acetic acid (NAA) or Indole-3-butyric acid (IBA) (0.1, 0.5 and 1.0 μM). The highest regeneration frequency (92 %) with multiple shoots (13.0 ± 1.15) and shoot length (4.23 ± 0.14 cm) was achieved on MS medium supplemented with 5.0 μM BA and 0.1 μM NAA after 8 weeks of culture. Further experiments were performed to test the effects of medium type, medium strength, pH and subculture passages on shoot induction and proliferation. An enhancement in average number of shoots (16.6 ± 0.45) per explant was obtained after four subculture passages. Micro shoots exhibited in vitro rooting on half strength MS medium containing 2.5 μM Indole-3-butyric acid (IBA) after 4 weeks of culture. The in vitro raised healthy plantlets with well-developed roots and shoots were successfully acclimatized in plastic cups containing sterile soilrite for 8 weeks under culture room conditions (150 PPFD) prior to field transfer. Through the acclimatization period (0–56 days), photosynthetic pigments (Chlorophyll a, b and Carotenoid content) decreased during the initial 2 weeks followed by significant increase during the successive period (21–56 days) of acclimatization. At the same time, all the tested antioxidant enzymes (SOD, CAT, APX and GR) exhibited an increasing trend throughout the acclimatization period. The culture room acclimatized plantlets were successfully established in earthen pots containing garden soil in greenhouse with 70 % survival rate.