A comprehensive review of recent developments in the gram-negative bacterial UDP-2,3-diacylglucosamine hydrolase (LpxH) enzyme.

The emergence of multidrug resistance has provided a great challenge to treat nosocomial infections, which have become a major health threat around the globe. Lipid A (an active endotoxin component), the final product of the Raetz lipid A metabolism pathway, is a membrane anchor of lipopolysaccharide (LPS) of the gram-negative bacterial outer membrane. It shields bacterial cells and serves as a protective barrier from antibiotics, thereby eliciting host response and making it difficult to destroy. UDP-2,3-diacylglucosamine pyrophosphate hydrolase (LpxH), a crucial peripheral membrane enzyme of the Raetz pathway, turned out to be the potential target to inhibit the production of Lipid A. This review provides a comprehensive compilation of information regarding the structural and functional aspects of LpxH, as well as its analogous LpxI and LpxG. In addition, apart from by providing a broader understanding of the enzyme-inhibitor mechanism, this review facilitates the development of novel drug candidates that can inhibit the pathogenicity of the lethal bacterium.

Identification of Protein Drug Targets of Biofilm Formation and Quorum Sensing in Multidrug Resistant Enterococcus faecalis.

Enterococcus faecalis (E. faecalis) is an opportunistic multidrug-resistant (MDR) pathogen found in the guts of humans and farmed animals. Due to the occurrence of (MDR) strain there is an urgent need to look for an alternative treatment approach. E. faecalis is a Gram-positive bacterium, which is among the most prevalent multidrug resistant hospital pathogens. Its ability to develop quorum sensing (QS) mediated biofilm formation further exacerbates the pathogenicity and triggers lifethreatening infections. Therefore, developing a suitable remedy for curing E. faecalis mediated enterococcal infections is an arduous task. Several putative virulence factors and proteins are involved in the development of biofilms in E. faecalis. Such proteins often play important roles in virulence, disease, and colonization by pathogens. The elucidation of the structure-function relationship of such protein drug targets and the interacting compounds could provide an attractive paradigm towards developing structure-based drugs against E. faecalis. This review provides a comprehensive overview of the current status, enigmas that warrant further studies, and the prospects toward alleviating the antibiotic resistance in E. faecalis. Specifically, the role of biofilm and quorum sensing (QS) in the emergence of MDR strains had been elaborated along with the importance of the protein drug targets involved in both the processes.

Synthesis, in vitro and structural aspects of benzothiazole analogs as anti-oxidants and potential neuroprotective agents.

Catalase, an important antioxidant enzyme, is known to have a neuroprotective role against neurodegenerative disorder. Earlier study has focussed on benzothiazole-triazole hybrid molecules that are larger in size and molecular weight and inhibit the amyloid ß (Aß)-catalase interaction thus aid in neuroprotection. Here we have synthesized the novel benzothiazole molecules with low molecular weight using One-pot methodology and assayed the neuroprotective effects of the synthesized compounds in the U87 MG cell line under H2O2 induced stressed condition and compared with other cell lines such as breast cancer (MCF-7) and macrophage (RAW-264.7) using cell viability assay. These analogs were found to enhance the neuronal cell viability and protect neuronal cells from the ROS mediated neuronal damage induced by H2O2. Furthermore, compounds 6a, 6b, 6c, 6d, and 7a modulate catalase and enhanced the catalase activity up to 90 % during the H2O2 exposure in the U87MG cell line. These analogs (6a, 6b, 6c and 6d) have exhibited strong binding energies of -7.39, -7.52, -6.5 and -7.1 as observed by molecular modeling studies using AutoDockTool-1.5.6. Lig Plot + program using potent analogs 6b and 6c and catalase enzyme indicated the presence of hydrophobic interactions in the catalytic site of catalase enzyme. Furthermore, a simulation study was conducted between ligand and catalase protein by DESMOND software that further strengthens these ligand and enzyme interactions. In silico ADMET study was conducted by the Swiss ADME program revealed the drug-likeliness of these analogs. The present study has identified benzothiazole analogs such as 6b, 6c and 6d have potential catalase modulating activity and is comparable with that of known drug Valproic acid, thus help in neuroprotection. This study can be further taken up for the in vivo animal model study for the possible therapy.