Harvinder Singh

The binding modes and binding affinities of artemisinin derivatives with Plasmodium falciparum Ca2+-ATPase (PfATP6)

Noncompetitive inhibitors of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) orthologue (PfATP6) of P. falciparum have important therapeutic value in the treatment of malaria. Artemisinin and its analogues are one such class of inhibitors which bind to a hydrophobic pocket located in the transmembrane region of PfATP6 near the biomembrane surface and interfere with calcium transport. The 3D structure of PfATP6 was modeled by homology modeling. A library consisting of 150 artemisinin analogues has been designed. Their molecular interactions and binding affinities with modeled PfATP6 protein have been studied using the docking, molecular mechanics based on generalized Born/surface area (MM-GBSA) solvation model and multi-ligand bimolecular association with energetics (eMBrAcE). Structure activity relationship models were developed between the antimalarial activity (log RA) and molecular descriptors like docking score and binding free energy. For both the cases the r2 was in the range of 0.538–0.688 indicating good data fit and

A case study: biomedical waste management practices at city hospital in Himachal Pradesh.

r_{cv}^2

Characterization and Screening of Native Scenedesmus sp. Isolates Suitable for Biofuel Feedstock.

was in the range of 0.525–0.679 indicating that the predictive capabilities of the models were acceptable. Besides, a scheme similar to linear response was used to develop free energy of binding (FEB) relationship based on electrostatic (∆Gele), van der Waal (∆GvdW) and surface accessible surface area (SASA), which can express the activity of these artemisinin derivatives. It has been seen that ∆GvdW has most significant correlation to the activity (log RA) and electrostatic energy (∆Gele) has less significant correlation. It indicates that the binding of these artemisinin derivatives to PfATP6 is almost hydrophobic. Low levels of root mean square error for the majority of inhibitors establish the docking, Prime/MM-GBSA and eMBrAcE based prediction model is an efficient tool for generating more potent and specific inhibitors of PfATP6 by testing rationally designed lead compound based on artemisinin derivatization.

The binding modes and binding affinities of epipodophyllotoxin derivatives with human topoisomerase IIα.

Total synthesis of podophyllotoxin is an expensive process and availability of the compound from the natural resources is an important issue for pharmaceutical companies that manufacture anticancer drugs. In order to facilitate reasoned scientific decisions on its management and conservation for selective breeding programme, genetic analysis of 28 populations was done with 19 random primers, 11 ISSR primers and 13 AFLP primer pairs. A total of 92.37 %, 83.82 % and 84.40 % genetic polymorphism among the populations of Podophyllum were detected using RAPD, ISSR and AFLP makers, respectively. Similarly the mean coefficient of gene differentiation (Gst) were 0.69, 0.63 and 0.51, indicating that 33.77 %, 29.44 % and 26 % of the genetic diversity resided within the population. Analysis of molecular variance (AMOVA) indicated that 53 %, 62 % and 64 % of the genetic diversity among the studied populations was attributed to geographical location while 47 %, 38 % and 36 % was attributed to differences in their habitats using RAPD, ISSR and AFLP markers. An overall value of mean estimated number of gene flow (Nm) were 0.110, 0.147 and 0.24 from RAPD, ISSR and AFLP markers indicating that there was limited gene flow among the sampled populations.

Genetic evaluation of ex situ conservation breeding projects of cheer pheasant (Catreus wallichii) and western tragopan (Tragopan melanocephalus) in India

Proper management of biomedical waste is a crucial issue for maintaining human health and the environment. The waste generated in the hospitals has the potential for spreading infections and causing diseases. The study was conducted by visiting a near by hospital in order to get acquainted with the generation of the biomedical waste and their disposal strategies. The study includes an assortment of details about the quantity of different types of waste generated, their handling, treatment, final disposal and various management strategies adopted by the hospital. The survey was conducted by asking various questions regarding the issue by the waste management team and the workers involved in managing the waste.

Application of the linear interaction energy method for rational design of artemisinin analogues as haeme polymerisation inhibitors

Quantitative structure–activity relationship (QSAR) analyses were performed independently on data sets belonging to two groups of insecticides, namely the organophosphates and carbamates. Several types of descriptors including topological, spatial, thermodynamic, information content, lead likeness and E-state indices were used to derive quantitative relationships between insecticide activities and structural properties of chemicals. A systematic search approach based on missing value, zero value, simple correlation and multi-collinearity tests as well as the use of a genetic algorithm allowed the optimal selection of the descriptors used to generate the models. The QSAR models developed for both organophosphate and carbamate groups revealed good predictability with r 2 values of 0.949 and 0.838 as well as values of 0.890 and 0.765, respectively. In addition, a linear correlation was observed between the predicted and experimental LD50 values for the test set data with r 2 of 0.871 and 0.788 for both the organophosphate and carbamate groups, indicating that the prediction accuracy of the QSAR models was acceptable. The models were also tested successfully from external validation criteria. QSAR models developed in this study should help further design of novel potent insecticides.

Mining simple sequence repeats in Picrorhiza kurroa transcriptomes for assessing genetic diversity among accessions varying for picrosides contents

In current study isolates of two native microalgae species were screened on the basis of growth kinetics and lipid accumulation potential. On the basis of data obtained on growth parameters and lipid accumulation, it is concluded that Scenedesmus dimorphus has better potential as biofuel feedstock. Two of the isolates of Scenedesmus dimorphus performed better than other isolates with respect to important growth parameters with lipid content of ~30% of dry biomass. Scenedesmus dimorphus was found to be more suitable as biodiesel feedstock candidate on the basis of cumulative occurrence of five important biodiesel fatty acids, relative occurrence of SFA (53.04%), MUFA (23.81%) and PUFA (19.69%), and more importantly that of oleic acid in its total lipids. The morphological observations using light and Scanning Electron Microscope and molecular characterization using amplified 18S rRNA gene sequences of microalgae species under study were also performed. Amplified 18S rRNA gene fragments of the microalgae species were sequenced, annotated at the NCBI website and phylogenetic analysis was done. We have published eight 18S rRNA gene sequences of microalgae species in NCBI GenBank.

Biocompatible synthesis of silver and gold nanoparticles using leaf extract of Dalbergia sissoo

Epipodophyllotoxin derivatives have important therapeutic value in the treatment of human cancers. These drugs kill cells by inhibiting the ability of topoisomerase II (TP II) to ligate nucleic acids that it cleaves during the double-stranded DNA passage reaction. The 3D structure of human TP IIα was modeled by homology modeling. A virtual library consisting of 143 epipodophyllotoxin derivatives has been developed. Their molecular interactions and binding affinities with modeled human TP IIα have been studied using the docking and Bimolecular Association with Energetics (eMBrAcE) developed by Schrödinger. Structure activity relationship models were developed between the experimental activity expressed in terms of percentage of intracellular covalent TP II-DNA complexes (log PCPDCF) of these compounds and molecular descriptors like docking score and free energy of binding. For both the cases the r2 was in the range of 0.624-0.800 indicating good data fit and r2(cv) was in the range of 0.606-774 indicating that the predictive capabilities of the models were acceptable. Low levels of root mean square error for the majority of inhibitors establish the docking and eMBrAcE based prediction model as an efficient tool for generating more potent and specific inhibitors of human TP IIα by testing rationally designed lead compounds based on epipodophyllotoxin derivatization.