Cytochrome bd oxidase: an emerging anti-tubercular drug target.

Cytochrome bd (cyt-bd) oxidase, one of the two terminal oxidases in the Mycobacterium tuberculosis (Mtb) oxidative phosphorylation pathway, plays an indispensable role in maintaining the functionality of the metabolic pathway under stressful conditions. However, the absence of this oxidase in eukaryotic cells allows researchers to select it as a potential drug target for the synthesis of anti-tubercular (anti-TB) molecules. Cyt-bd inhibitors have often been combined with cytochrome bcc/aa3 super-complex inhibitors in anti-TB drug regimens to achieve a desired bactericidal response. The functional redundancy between both the terminal oxidases is responsible for this. The cryo-EM structure of cyt-bd oxidase from Mtb (PDB ID: 7NKZ) further accelerated the research to identify its inhibitor. Herein, we have summarized the reported anti-TB cyt-bd inhibitors, insight into the rationale behind targeting cyt-bd oxidase, and an outline of the architecture of Mtb cyt-bd oxidase.

Fe3 C/Fe Decorated N-doped Carbon Derived from Tetrabutylammonium tetrachloroferrate Complex as Bifunctional Electrocatalysts for ORR, OER and Zn-Air Batteries in Alkaline Medium.

The emergence of non-precious metal-based robust and economic bifunctional oxygen electrocatalysts for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is crucial for the rational design of commercial rechargeable Zn-air batteries (RZAB) with safe energy conversion and storage systems. Herein, a facile strategy to fabricate a cost-efficient, bifunctional oxygen electrocatalyst Fe3 C/Fe decorated N doped carbon (FeC-700, the catalyst prepared at carbinization temperature of 700 °C) with a unique structure has been developed by carbonization of a single source precursor, tetrabutylammonium tetrachloroferrate(III) complex. The ORR and OER activity revealed excellent performance (ΔE=0.77 V) of the FeC-700 electrocatalyst, comparable to commercial Pt/C and RuO2, respectively. The designed temperature-tuneable structure provided sufficiently accessible active sites for the continuous passage of electrons by shortening the mass transfer pathway, leading to extremely durable electrocatalysts with high ECSA and amazing charge transfer performance. Remarkably, the assembled Zn-air batteries with the FeC-700 catalyst as the bifunctional air electrode delivers gratifying charging-discharging ability with an impressive power density of 134 mW cm-2 with a long lifespan, demonstrating prodigious possibilities for practical application.

Visible light induced regioselective C-3 thiocyanation of imidazoheterocycles through naphthalimide dye based photoredox catalysis.

A visible light induced C-3 thiocyanation of imidazo[1,2-a]pyridines by using a naphthalimide based photoredox catalyst has been reported. Tolerance of electron withdrawing and donating groups at different positions of the imidazo[1,2-a]pyridine ring led to a wide substrate accessibility of this method. This methodology is further reproducible with other heterocycles like benzo[d]imidazo[2,1-b]thiazoles, indoles, azaindoles, and anilines.

Ni(II)-Incorporated Ethylene Glycol-Linked Tetraphenyl Porphyrin-Based Covalent Organic Polymer as a Catalyst for Methanol Electrooxidation.

Methanol oxidation reaction (MOR) is a perfect alternative to the conventional oxygen evolution reaction (OER), generally utilized as the anode reaction for hydrogen generation via the electrochemical water splitting method. Moreover, MOR is also relevant to direct methanol fuel cells (DMFCs). These facts motivate the researchers to develop economical and efficient electrocatalysts for MOR. Herein, we have introduced an ethylene glycol-linked tetraphenyl porphyrin-based (EG-POR) covalent organic polymer (COP). The Ni(II)-incorporated EG-POR material Ni-EG-POR displayed excellent OER and MOR activities in an alkaline medium. The materials were thoroughly characterized using 13C solid-state NMR, Fourier transform infrared spectroscopy (FT-IR), Brunauer-Emmett-Teller (BET) surface area analyzer, X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), thermogravimetric analyzer (TGA), and powder X-ray diffraction (PXRD) techniques. These organic-inorganic hybrid materials showed high chemical and thermal stability. Ni-EG-POR requires an overpotential of 400 mV (vs RHE) in OER and 190 mV (vs RHE) in MOR to achieve a current density of 10 mA cm-2. In addition, the catalyst also showed excellent chronoamperometric and chronopotentiometric stability, indicating that the catalyst can provide stable current over a longer period and its potential as a non-noble metal MOR catalyst.

Copper Immobilized over 2D Hexagonal SBA-15 for Electrochemical and Colorimetric Sulfite Sensing.

Sulfite (SO32-) is considered a highly toxic anion for living organisms. Herein, we report the synthesis of copper immobilized over a 2D hexagonally ordered mesoporous silica material CuMS as an electrochemical and colorimetric dual-technique-based sensing platform for sulfite detection. The immobilization of copper on silica was achieved through the bis[3-(triethoxysilyl)propyl]tetrasulfide (TEPTS) ligand. Morphological and physical properties of the material were confirmed by several characterization techniques, including scanning electron microscopy, transmission electron microscopy, X-ray diffraction, N2 sorption, and X-ray photoelectron spectroscopy. The CuMS material retained mesoporosity with a narrow pore size distribution (D ≈ 5.4 nm) and a high Brunauer-Emmett-Teller surface area of 682 m2 g-1 after the immobilization of copper. The prepared catalyst shows promising electrocatalytic activity toward sulfite oxidation. A linear variation in the peak current was obtained for SO32- oxidation in the 0.2-15 mM range with a high sensitivity of 62.08 µA cm-2, under optimum experimental conditions. The limit of detection (LOD) was found to be 1.14 nM. CuMS also shows excellent activity toward colorimetric detection of sulfite anions with an LOD of 0.4 nM. The proposed sensor shows high selectivity toward the sulfite anion, even in the presence of common interferents. The detection of sulfite in white wine with excellent recovery demonstrates the practical applicability of this sensor.

Quality of Online Information for Esophageal Cancer.

The Internet is a readily available source of information, and patients in North America frequently access it. Esophageal cancer is the 7th most common cancer worldwide, but there is a lack of studies examining esophageal cancer website quality. This current study looks to systematically analyze the quality of websites accessed by patients with esophageal cancer. A previously validated website evaluation tool was used to analyze the quality of online esophageal cancer resources for patients. The term "esophagus cancer" was used to retrieve hits from the search engine Google and the meta-search engines Dogpile and Yippy. A 100 website list was compiled using pre-specified inclusion and exclusion criteria. Websites were evaluated regarding administration, accountability, authorship, organization, readability, content, and accuracy. The term "esophagus cancer" returned over 500 websites from the search engines. Of the 100 websites included for analysis, 97% disclosed ownership, sponsorship, and advertising. Only 35% identified an author and even fewer (31%) gave the author's credentials. Only 31% declared updates to their information within the past 2 years. Readability scores revealed only 9%, and 12% of sites scored at an elementary level, according to the Flesch-Kincaid (FK) and SMOG scoring scales, respectively. The average FK and SMOG scores were 12.6 and 11.0, respectively. Detection was the most accurately described (70%). However, few websites provided accurate incidence/prevalence (28%), stage-specific prognosis (27%), or preventative information (17%). The quality of websites offering information on esophageal cancer is variable. While they overwhelmingly disclose website ownership interests, most do not identify authors, poorly describe important domains of esophageal cancer, and overall readability exceeds the commonly accepted level for non-healthcare professionals.

New structural classes of antimalarials.

Malaria remains a major vector borne disease claiming millions of lives worldwide due to infections caused by Plasmodium sp. Discovery and development of antimalarial drugs have previously been dominated majorly by single drug therapy. The malaria parasite has developed resistance against first line and second line antimalarial drugs used in the single drug therapy. This has drawn attention to find ways to alleviate the disease burden supplanted by combination therapy with multiple drugs to overcome drug resistance. Emergence of resistant strains even against the combination therapy has now mandated the revision of the current antimalarial pharmacotherapy. Research efforts of the past decade led to the discovery and identification of several new structural classes of antimalarial agents with improved biological attributes over the older ones. The following is a comprehensive review, addressed to the new structural classes of heterocyclic and natural compounds that have been identified during the last decade as antimalarial agents. Some of the classes included herein contain one or more pharmacophores amalgamated into a single bioactive scaffold as antimalarial agents, which act upon the conventional and novel targets.

Isatin: A Scaffold with Immense Biodiversity.

Isatin is an endogenous and a significant category of fused heterocyclic components and has widely been a part of several potential biologically useful synthetics. Since its discovery, tons of research work has been conducted with respect to the synthesis, chemical properties, and biological and industrial applications. It contains an indole nucleus having both lactam and keto moiety, which, while being a part of a molecular framework, exerted several biological effects, viz.; anti-microbial, anti-tubercular, anticonvulsant, anti-cancer, etc. Isatin derivatives are synthetically significant substrates, which can be utilized for the synthesis of huge diversified chemical entities of which few members emerged as drugs. The reason for this review is to provide extensive information pertaining to the chemistry and its significance in altering several pathological states of isatin and its derivatives. A Structure-Activity Relationship study thus developed through a gamut of scientific information indicates the importance of mostly electron-withdrawing groups, halogens, nitro, alkoxy, and, to a minor extent, groups with positive inductive effects, such as methyl at position 1, 5, 6 and 7 of isatin in alleviating several clinical conditions. It is also observed from the survey that the presence of two oxo groups at positions 2 and 3 sometimes becomes insignificant as a fusion with a heterocycle at these positions resulted in a biologically relevant compound.

pH Sensitive Interpenetrating Network Bio Containers of Gum Ghatti for Sustained Release of Glipizide.

OBJECTIVE: A novel natural polymer, Gum Ghatti (GG) was explored to develop a new polymeric system that will combine the biodegradable and biocompatible properties of GG and mechanical properties of poly vinyl alcohol (PVA) for drug delivery application. METHODS: Smart pH sensitive, porous, glutaraldehyde (GA) crosslinked interpenetrating network (IPN) microspheres loaded with glipizide were developed by the emulsion crosslinking method. The drug entrapment efficiency was 92.85±1.5%. FTIR confirmed the formation of IPN structure. Drug release can be extended upto 7 hours by modulating the concentration of crosslinking agent. Swelling study and diffusion co-efficient (D) of water transport were performed in order to understand the phenomenon of water penetration through the microsphere. In vivo antidiabetic activity performed on alloxane induced diabetic rats indicated that in case of pure glipizide sudden reduction of elevated blood glucose was observed after 3 hours. RESULTS: In case of rats treated with glipizide loaded IPN microparticles, the initial percentage reduction of blood glucose level was slow within the first 3 hours of administration, as compared to pure glipizide but after 6 hours 90% reduction was observed which confirmed sustained release nature of microspheres. CONCLUSION: Thus IPN microparticles were found suitable for sustained delivery of BCS class II drug glipizide.