Plasmepsin inhibitors: design, synthesis, inhibitory studies and crystal structure analysis

Plasmepsin group of enzymes are key enzymes in the life cycle of malarial parasites. As inhibition of plasmepsins leads to the parasite's death, these enzymes can be utilized as potential drug targets. Although many drugs are available, it has been observed that Plasmodium falciparum, the species that causes most of the malarial infections and subsequent death, has developed resistance against most of the drugs. Based on the cleavage sites of hemglobin, the substrate for plasmepsins, we have designed two compounds (p-nitrobenzoyl-leucine-β -alanine and p-nitrobenzoyl-leucine-isonipecotic acid), synthesized them, solved their crystal structures and studied their inhibitory effect using experimental and theoretical (docking) methods. In this paper, we discuss the synthesis, crystal structures and inhibitory nature of these two compounds which have a potential to inhibit plasmepsins

Mycobacterium abscessus Glycopeptidolipid Prevents Respiratory Epithelial TLR2 Signaling as Measured by HβD2 Gene Expression and IL-8 Release

Mycobacterium abscessus has emerged as an important cause of lung infection, particularly in patients with bronchiectasis. Innate immune responses must be highly effective at preventing infection with M. abscessus because it is a ubiquitous environmental saprophyte and normal hosts are not commonly infected. M. abscessus exists as either a glycopeptidolipid (GPL) expressing variant (smooth phenotype) in which GPL masks underlying bioactive cell wall lipids, or as a variant lacking GPL which is immunostimulatory and invasive in macrophage infection models. Respiratory epithelium has been increasingly recognized as playing an important role in the innate immune response to pulmonary pathogens. Respiratory epithelial cells express toll-like receptors (TLRs) which mediate the innate immune response to pulmonary pathogens. Both interleukin-8 (IL-8) and human β-defensin 2 (HβD2) are expressed by respiratory epithelial cells in response to toll-like receptor 2 (TLR2) receptor stimulation. In this study, we demonstrate that respiratory epithelial cells respond to M. abscessus variants lacking GPL with expression of IL-8 and HβD2. Furthermore, we demonstrate that this interaction is mediated through TLR2. Conversely, M. abscessus expressing GPL does not stimulate expression of IL-8 or HβD2 by respiratory epithelial cells which is consistent with “masking” of underlying bioactive cell wall lipids by GPL. Because GPL-expressing smooth variants are the predominant phenotype existing in the environment, this provides an explanation whereby initial M. abscessus colonization of abnormal lung airways escapes detection by the innate immune system

Diphosphazanes as ligands: links betwen phospeorus ceiwistry and organohetallic cejmistry

The reactivity of several new acyclic, cyclic and bicyclic diphosphazanes towards Group-6 metal and iron carbonyls, and Pd, Pt and Rh derivatives has been studied. The structures of the products have been elucidated by IR and NMR spectroscopy and confirmed in a few instances by single crystal X-ray analyses

Zinc-catalyzed reduction of imines by triethylsilane

Low-cost zinc is employed as a catalyst along with triethylsilane (TES) in a simple, straightforward, chemoselective reduction of various aldimines and ketimines to the corresponding secondary amines at room temperature and pressure

Apical versus equatorial disposition of substituents in tetraoxyphosphoranes bearing a 1,3,2-dioxaphosphocin ring: Implications on apicophilicity in trigonal bipyramidal phosphorus

10.1021/ic010935wInorganic Chemistry4192356-2363INOC

Perception and attitudes towards information and communication technology (internet) for purchase decisions among generation cohorts

Online retailers are proliferating in huge numbers and they have observed a shift in the trend of consumers making buying decisions virtually over buying in brick and mortar retailers. There are various factors which is influencing this change of pattern. The generation cohort groups referred to as Gen X and Gen Y in the study refers to the group who belong to same age group, who share common beliefs, values, attitudes and who share common experiences during their life cycle. It is been considered as one of the basis for market segmentation (Kotler, 2000). Consumer continuously unlearns and learns based on his experiences in making purchase decisions. As technology advances and there are new ways of selling and buying, consumer evolves himself and the whole trend changes. The mind set of people born in different generations differs [19]. Though the internet purchases are slowly increasing, because of the media and negative publicity of a few bad experiences, consumers especially the Generation X category lack the trust and confidence to go a step ahead and shop online. To understand the deeper behaviour of consumers of different generations, this study makes an attempt to understand the perceptions and attitudes of different generation groups towards information and communication technology (ICT) for buying decisions. It becomes important for the online marketers to understand this diversified market segments so that they can respond with suitable strategies and can further capture the market share. The current paper is designed to yield results on awareness, perception, and attitude of different generations towards the information and communication technology for buying decisions. The study was carried out in Bangalore City with the sample size of 100 respondents using stratified sampling technique. The Hypothesis was proposed for the variables under study and tested. The data collected were analyzed using chi-square test and two population t test