Ashutosh Mani

Crystal structure of 2,5-di­methyl­anilinium salicylate

The title molecular salt, C8H12N+·C7H5O3 − arose from the proton-transfer reaction between 2,5-xylidine and salicylic acid. In the anion, the dihedral angle between the planes of the aromatic ring and the –CO2 − group is 11.08 (8)°; this near planarity is consolidated by an intramolecular O—H⋯O hydrogen bond. In the crystal, the components are connected by N—H⋯O hydrogen bonds, with all three O atoms in the anion acting as acceptors; the result is a [100] chain. The structure also features weak C—H⋯O bonds and aromatic π–π stacking [centroid-to-centroid distance = 3.7416 (10) Å] interactions, which lead to a three-dimensional network.

Structure based virtual screening for identification of potential quorum sensing inhibitors against LasR master regulator in Pseudomonas aeruginosa

Inter and intracellular communication in bacteria, which is known as quorum sensing (QS), is mediated by small diffusible signaling molecules known as autoinducers. QS regulates various virulence factors responsible for pathogenesis. Increasing resistance of microorganisms against traditional antibiotics has turned the focus towards the QS as it exerts less selective pressure preventing development of resistance among microorganisms. LasR, a transcription factor that controls QS in Pseudomonas aeruginosa, is an attractive therapeutic target for inhibitors. This study aimed to screen natural compounds as potential inhibitors of LasR. About 2603 compounds from ZINC database were virtually screened against the structure of LasR. Then after qualifying compounds were filtered on the parameters of Lipinskis rule and ADME. Six novel potential QS inhibiting compounds were selected on the basis of binding energy. Structures of LasR-ligand complexes were analysed to have insight of binding between inhibitors and target. It is pertinent to mention here that all the molecules are structurally different from 3-oxo-C12HSL,a native autoinducer of LasR, that play key role in formation of LasR dimer which is an active form of the protein to facilitate QS.

Structure prediction and docking-based molecular insights of human YB-1 and nucleic acid interaction

Y-box-binding protein 1 (YB-1), a cold shock domain protein, is one of the most conserved nucleic acid-binding proteins. The multifunctional human YB-1 is a member of a large family of proteins with an evolutionary ancient cold shock domain. The presence of a cold shock domain is a specific feature of Y-box-binding proteins and allows attributing them to a wider group of proteins containing a cold shock domain. This protein is involved in a number of cellular processes including proliferation, differentiation and stress response. The YB-1 performs its function both in the cytoplasm and in the cell nucleus. In this study, we present the structure of full-length human YB-1 protein along with investigation of their nucleic acid-binding preferential. The study also focuses on biases for particular purine and pyrimidine bases. The overall goal of this study was to model and validate full-length YB-1 protein and to compare its nucleic acid-binding studies with previous reports.

Anticancer Activity of Herbal Medicine: Mechanism of Action

Cancer is an alarming disease and quite lethal in nature in developed and developing nations. Many new therapeutic agents and therapies are available in the market but have some severe side effects on human beings’ organs. These therapeutic agents are quite costly and not easily available in some of the developing nations. Various scientific reports have shown that chemoprevention through naturally derived herbal and dietary phytochemicals is an innovative therapeutic tool against different cancer types. These herbal phytochemicals have shown their potential anticancer activity in both in vitro and in vivo studies. Further, many of them have been successfully proved for their chemopreventive property by inducing apoptosis equivalent to certain other chemical drugs without causing any side effects. The combinational role of herbal and dietary phytochemicals has proved to be very effective against cancer prevention. The present chapter summarised the effectiveness of herbal and dietary phytochemicals for chemoprevention and also highlighted their combinational role on various kinds of cancer.

Comparative genomic analysis of Rickettsia rickettsii for the identification of drug and vaccine targets: tolC as a proposed candidate for case study

BACKGROUND Antibiotic resistance is increasing rapidly in pathogenic organisms, creating more complications for treatment of diseases. Rocky Mountain spotted fever (RMSF) is a neglected tropical disease in humans caused by Rickettsia rickettsii for which no effective therapeutic is available. Subtractive genomics methods facilitate the characterization of non-homologous essential proteins that could be targeted for the discovery of potential therapeutic compounds against R. rickettsii to combat RMSF. Present study followed an in-silico based methodology, involving scanning and filtering the complete proteome of Rickettsia rickettsii by using several prioritization parameters in the search of potential candidates for drug development. Further the putative targets were subjected to series of molecular dockings with ligands obtained from PDB ligand database to identify suitable potential inhibitors. The comparative genomic analysis revealed 606 non-homologous proteins and 233 essential non-homologous proteins of R. rickettsii. The metabolic pathway analysis predicted 120 proteins as putative drug targets, out of which 56 proteins were found to be associated with metabolic pathways unique to the bacteria and further subcellular localization analysis revealed that 9 proteins as potential drug targets which are secretion proteins, involved in peptidoglycan biosynthesis, folate biosynthesis and bacterial secretion system. As secretion proteins are more feasible as vaccine candidates, we have selected a most potential target i.e. tolC, an outer membrane efflux protein that belongs to type I secretion system and has major role in pathogen survival as well as MDR persistence. So for case study, we have modelled the three dimensional structure of tolC (tunnel protein). The model was further subjected to virtual screening and in-silico docking. The study identified three potential inhibitors having PDB Id 19V, 6Q8 and 39H. Further we have suggested that the above study would be most important while considering the selection of candidate targets and drug or vaccine designing against R. rickettsii.

Binding preferential of chickpea cold shock protein during nucleic acid interactions

Cold shock proteins (CSPs) have a widespread occurrence from prokaryotes to eukaryotes including plants. These proteins are known to possess nucleic acid binding properties. CSPs have a single cold shock domain in prokaryotes while N-terminal and C-terminal flanking regions are present in eukaryotic CSPs. The objective of this study was to investigate nucleic acid binding preferential for the chickpea CSP. Full cDNA of chickpea CSP was cloned and sequenced. The sequence was submitted to GenBank (accession no. KM036036) at NCBI. Multiple sequence alignment and phylogenetic analysis further revealed that the inferred amino acid sequence belongs to CSP family. Molecular docking was performed between the CSP and variety of nucleic acids entities. These results suggest that CSPs of chickpea possess preferential binding affinity for single stranded nucleic acids. Docking results suggest that homo-polymer entities of RNA polyU RNA (20mer) form most stable complex.

Bioinformatics-based study on prokaryotic, archaeal and eukaryotic nucleic acid-binding proteins for identification of low-complexity and intrinsically disordered regions

ABSTRACT Intrinsically disordered regions (IDRs) and low-complexity regions (LCRs) in transcription factors (TFs) are known to be key players in various cellular functions. Conformational flexibility of these regions allows them to recognize and interact with a large number of molecules. Previous studies show that certain TFs which are related to environmental response are significantly enriched in IDRs and LCRs. It has been proposed that all organisms in response to environmental conditions use these IDRs and LCRs for introducing versatility in the interactions in biological processes to quickly adapt and respond to challenging environmental conditions. A comparative study has been conducted on these regions to measure the average abundance of LCRs and IDRs in different types of TFs. In this project we have identified the IDRs and LCRs in prokaryotic, eukaryotic and archaeal TFs by using bioinformatics and compared them for average density of IDRs and LCRs.

Solubility, thermal, photoconductivity and laser damage threshold studies on L-serine acetate (LSA) single crystal

L-serine acetate crystal was grown by slow evaporation technique. Solubility of L-Serine Acetate was determined at different temperatures. L-Serine Acetate was characterized by SEM is to identify the morphology of the crystal. TG and DTA study reveals the thermal stability of the grown crystal. Dielectric measurement was carried out for different temperature ranges. Photo conductivity study revealed the nature of conductivity of the crystal under halogen light. Laser damage threshold of the crystal was measured using Nd:YAG laser source. NLO property of the crystal is confirmed by Kurtz-Perry powder technique.