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This study aims to investigate the potential of mixing jackfruit seed flour (JFSF) with pasta and its effects on techno-functional properties, cooking behavior, textural characteristics, morphology, macromolecular interactions, and secondary structure of proteins of pasta. The results showed with increase in the addition of JFSF from 6 to 24% caused significant (P < 0.05) improvement in the functional properties, decline in the minimum cooking time (7.07 to 6.20 min), and an increase in the cooking loss (5.13 to 11.26%) as well as firmness of the pasta. Organoleptic evaluations indicated the incorporation of JFSF up to 18% without affecting the flavor. Scanning electron microscopy revealed that after cooking bell-shaped starch granules were embedded in the protein matrix. Fourier transform infrared spectra analysis of the secondary structure of protein showed that the major protein fractions were β-sheets, followed by β helix. Positive correlations between cooking losses and water solubility index and several other parameters were established using principal component analysis. Therefore, incorporating JFSF into pasta could be a promising way for developing protein-rich, high-quality pasta with improved nutritional and functional properties.

The influence of semolina replacement with wheatgrass powder (WGP; 3%-15%) was evaluated with reference to nutritional, techno-functional, phytochemical, textural, and structural characteristics of functional pasta. Results showed that incorporation of WGP significantly (p 0.05) decreased the pasting viscosity of flour blends, while it increased the water and oil absorption capacity and water solubility index. Increased levels of WGP significantly decreased the optimum cooking time from 6.00 to 4.22 min but increased the cooking loss (2.83%-4.36%). Enrichment of pasta with WGP significantly (p 0.05) enhanced the protein (12.16-17.33 g/100 g), fiber (1.21-4.60 g/100 g), antioxidant activities in terms of DPPH, FRAP, and ABTS. The total phenolic and flavonoid content increased from 56.20-253.90 mg GAE/100 g to 47.41-202.90 mg QE/100 g in the functional pasta. Addition of WGP significantly (p 0.05) decreased the lightness (L*) while the greenness (-a*) of the pasta increased progressively owing to the total chlorophyll pigment. The firmness and toughness of the pasta increased up to 9% WGP level and decreased further, owing to the interaction between WGP protein and fiber with gluten protein matrix as evident from scanning electron microscopy (SEM). Furthermore, the cooking of pasta results in a significant reduction in all the components in comparison to uncooked pasta. Fourier transform infrared (FTIR) spectroscopy further confirmed the presence of phenols, flavonoids, and chlorophyll in WGP-incorporated pasta. Overall acceptability scores of pastas with 9% WGP were found to have the highest (7.57), and with an increase in a further level of WGP, sensory scores decreased (6.55). Moreover, the principal component analysis also compliments the sensory results for 9% WGP-incorporated pasta.

The present study investigated the effect of honey and extrusion processing parameters on techno-functional and bioactive properties of whole-grain corn flour breakfast cereals. The central composite rotatable design (CCRD) was used to plan the experiments using feed moisture (FM), extrusion temperature (ET), and honey level as process variables and sectional expansion ratio (SER), bulk density (BD), water absorption index (WAI), water solubility index (WSI), and textural hardness as response variables. The feed containing honey and whole-grain corn flour was extruded through a twin-screw extruder according to CCRD. The data were fit to the appropriate regression models based on model significance and insignificant lack of fit. The selected experiments from CCRD were considered for studying the bioactive properties, and the effect of ET and honey level on bioactive properties was determined. The results of the study indicated that FM and honey adversely affected the SER, BD, and textural hardness, while ET augmented these properties of breakfast cereals. The WAI decreased with an increase in honey level and ET during extrusion. The incremental addition of honey in the mix as well extrusion at elevated temperature led to higher WSI. The whole-grain corn flour added with 10.22% honey and extruded at 16.06% FM, and 138.07°C ET produced optimum quality breakfast cereals with 0.70 desirability. The total phenolic content of breakfast cereals decreased, and antioxidant activity and hydroxymethylfurfural content increased upon extrusion at the higher temperatures. Honey addition lowers the loss of phenolic content during extrusion and improves the antioxidant activity of breakfast cereals.

Suitability of protein isolates recovered from pangas processing waste was explored for supplementing pasta and influence of supplementation was evaluated on the protein digestibility, textural, morphological and sensory characteristics. Results showed that addition of pangas protein isolates (PPI) significantly (p 0.05) change in the sensory attributes of PPI supplemented pasta was observed. However, intensity of fish flavour increased in the pasta from 1.5 to 4.4 with increased PPI levels. Among different level tested, pasta supplemented with 5.0 g 100 g−1 isolates gave better sensory scores and low fish flavour intensity in pasta.

Shifting toward a plant-based diet from an animal-based diet is good approach to tackle nutritional and health issues. Legumes are an important food source and play a significant role in the nutritional well-being of the population (Punia et al., 2019). Kidney beans (Phaseolus vulgaris L.) also known as common beans are an economical and staple food legume for devolving countries as it provides adequate nutrition to the diet. Kidney beans stand out as a source of complex carbohydrates (50–60%), protein (20–25%), and dietary fiber, along with a good amount of minerals and vitamins. Among the complex carbohydrates, starch is the major storage polysaccharide, accounting for 20–45% depending upon the cultivar. The starch of kidney beans possesses unique properties as it has higher levels of resistant starch contents and lower levels of rapidly digestible starch content, which accounts for its low glycemic index (GI) response and positive impact on human health. Proteins are normally considered as the prominent macronutrient in red kidney beans with globulins (65% w/w), albumins (15% w/w), glutelins (10% w/w), and prolamins (2% w/w) being the principal protein components. Kidney beans also contain a variety of phenolic compounds (polyphenols, flavonoids, tocopherols, unsaturated fatty acids, and peptides) that serve as the major antioxidants and play a key role in reducing the reactive oxygen species that cause cellular and molecular damages. Complex chemical composition and presence of bioactive compounds in kidney beans account for various biological activities, which include antimicrobial, antioxidant, antihyperglycemic, and anticancer effects and also lower the occurrence of chronic noncommunicable diseases such diabetes, cancer, obesity diabetics, coronary heart disease, cardiovascular diseases, and neurodegenerative disorders due to the protective physiological effects conferred by the chemical constituents of the kidney bean. This chapter will provide an insight to the nutritional potential of the kidney bean along with its antioxidant compounds, bioactive components, and health benefits and its application formulation of conventional and nonconventional food products.

The adzuki bean (Vigna angularis) is a legume crop that has a sweet and nutty flavor. It is a good source of protein, essential fatty acids, fiber, minerals (especially calcium and iron), and phytochemicals such as polyphenols and phytates. The lipid fraction has a good amount of unsaturated essential fatty acids and has low amounts of saturated fatty acids. It contains approximately 7.5% protein with a good amino acid profile, which, when combined with cereals, proves to have a crucial role in fulfilling the dietary requirements of protein more significantly in less developed countries. The bioactive compounds in adzuki beans have also drawn significant interest due to its antioxidant properties and cytoprotective effects owing to high tocopherol and flavonoids content, which add on to its nutritional profile. Many phytochemicals and extracts found in Adzuki beans are known to have functional properties such as antimicrobial, anti-inflammatory, antidiabetic, renal protection, hepatoprotective, antihypertensive, and anti hyperlipidemic effects. The use of adzuki beans for health promotion and disease prevention is promising due to its nutritional and functional properties and presents immense potential to be considered as a functional food. They are used in several food products such as traditional snacks, sweets, ingredients in bakery products, and meat extenders.

We report the biological evaluation of 5-(5-nitrothiophen-2-yl)-4,5-dihydro-1H-pyrazole derivatives against bacteria, eukaryotic cell lines and the assessment of their mechanisms of action to determine their prospects of being developed into potent antituberculosis agents. The compounds were evaluated for their antibacterial property against Mycobacterium tuberculosis H37Rv, multidrug-resistant M. tuberculosis, Mycobacterium bovis BCG, Mycobacterium aurum, Escherichia coli, and Staphylococcus aureus using high-throughput spot-culture growth inhibition assay. They were found to be selective toward slow-growing mycobacteria and Gram-positive bacteria. In M. bovis BCG, they exhibited a bactericidal mode of action. Cytotoxicity was assessed in human THP-1 and murine RAW 264.7 cell lines, and the compounds showed a lower cytotoxicity potential when compared with their antibacterial activity. They were found to be excellent whole-cell efflux pump inhibitors of the mycobacterial surrogate M. aurum, performing better than known efflux pump inhibitor verapamil. The 5-nitrothiophene moiety was identified for the first time as a prospective inhibitor scaffold of mycobacterial arylamine N-acetyltransferase enzyme, which is the key enzyme in metabolizing isoniazid, a first-line antituberculosis drug. The two aforementioned findings make the compounds potential hits in the development of adjunctive tuberculosis therapy.

In this study, protein isolate obtained from Pangas processing waste (PPI) was incorporated into pasta at different levels (0, 2.5, 5.0, 7.5 and 10.0 g/100 g). After that, the nutritional, functional, cooking and sensory characteristics of PPI supplemented pasta were extensively investigated. The addition of PPI content from 0 to 10.0 g/100 g increased the protein content of pasta from 11.76 g/100 g–21.30 g/100 g (p 0.05). Though the PPI supplementation caused some quality changes in the pasta, it improved the color as well as a nutritional profile of pasta. Based on this study, it can be concluded that the incorporation of PPI into pasta could produce nutritional enriched pasta with good color and functionality.

Brown rice was germinated for different times (12, 24, 36, and 48 h) at different temperatures (25, 30, and 35 °C) with the aim to improve the in vitro digestibility and antioxidant potential of the flour made from it. Results showed that increase in germination time and temperature increased in vitro digestibility of starch and protein during germination of brown rice owing to depolymerisation of starch and protein molecules by enzymatic activity. After germination under varying conditions, antioxidant activity increased from 50.19 to 95.58%, total phenolic and flavonoid contents from 0.88 to 2.02 mg GAE/g and 34.06–62.94 mg QE/100g, respectively. Germination at elevated temperature (35 °C) for prolonged time (48 h) also increased the reducing power by 60.49% and metal chelating activity by 114.50% as a result of structural breakdown of bound phenolics. Increased activity of hydrolytic enzymes with progress in the germination time and temperature also results in continuous reduction in the pasting properties and lightness values (L), while increasing a* and b* values of the flour of germinated brown rice. Tailored germination, therefore, can be offered as a tool to increase nutrient digestibility and bioactive potential of brown rice as compared to non-germinated brown rice, thus, producing naturally modified flour with enhanced functionality.

Objectives Identification and validation of novel therapeutic targets is imperative to tackle the rise of drug resistance in tuberculosis. An essential Mur ligase-like gene (Rv3712), expected to be involved in cell-wall peptidoglycan (PG) biogenesis and conserved across mycobacteria, including the genetically depleted Mycobacterium leprae, was the primary focus of this study. Methods Biochemical analysis of Rv3712 was performed using inorganic phosphate release assays. The operon structure was identified using reverse-transcriptase PCR and a transcription/translation fusion vector. In vivo mycobacterial protein fragment complementation assays helped generate the interactome. Results Rv3712 was found to be an ATPase. Characterization of its operon revealed a mycobacteria-specific promoter driving the co-transcription of Rv3712 and Rv3713. The two gene products were found to interact with each other in vivo. Sequence-based functional assignments reveal that Rv3712 and Rv3713 are likely to be the mycobacterial PG precursor-modifying enzymes MurT and GatD, respectively. An in vivo network involving Mtb-MurT, regulatory proteins and cell division proteins was also identified. Conclusions Understanding the role of the enzyme complex in the context of PG metabolism and cell division, and the implications for antimicrobial resistance and host immune responses will facilitate the design of therapeutics that are targeted specifically to M. tuberculosis.

Gluten Free bread is gaining popularity these days due to the upsurge cases of gluten intolerance. But, development of gluten bread is itself a challenge due to the absence of gluten, which is well known as a heart of bread. Additives can be added to overcome these challenges but again, due to their chemical origin, their use is limited. To overcome such issue and to maintain the acceptability of gluten free bread among consumers technological modifications are carried out in the food processing industry by various techniques like enzymatic modification, high pressure processing, sourdough fermentation, extrusion technology, germination, heat treatment, hydrothermal treatment etc.

Wheat grains were germinated at different time (12, 24, 36, and 48 h) and temperature (25, 30, and 35°C) to enhance the functionality of resultant flour. Results revealed that an increase in germination time and temperature enhanced the in vitro digestibility of starch (10.35–42.30 %) and proteins (6.31–44.02 %) owing to their depolymerization by hydrolytic enzymes. Total phenolic and flavonoid content of wheat during germination at variable conditions were enhanced significantly (p

In this study, the inhibitory potential of 3-(5-nitrofuran-2-yl)prop-2-en-1-one derivatives was evaluated against a panel of bacteria, as well as mammalian cell lines to determine their therapeutic index. In addition, we investigated the mechanism of antibiotic action of the derivatives to identify their therapeutic target. We discovered compound 2 to be an extremely potent inhibitor of Mycobacterium tuberculosis H37Rv growth (MIC: 0.031 mg/L) in vitro, performing better than the currently used first-line antituberculosis drugs such as isoniazid, rifampicin, ethambutol, and pretomanid in vitro. Furthermore, compound 3 was equipotent to pretomanid against a multidrug-resistant M. tuberculosis clinical isolate. The derivatives were selective and bactericidal towards slow-growing mycobacteria. They showed low cytotoxicity towards murine RAW 264.7 and human THP-1 cell lines, with high selectivity indices. Compound 1 effectively eliminated the intracellular mycobacteria in a mycobacteria-infected macrophage model. The derivatives were assessed for their potential to inhibit mycobacterial arylamine N-acetyltransferase (NAT) and were identified as good inhibitors of recombinant mycobacterial NAT, a novel target essential for the intracellular survival of M. tuberculosis. This study provided hits for designing new potent and selective antituberculosis leads, having mycobacterial NAT inhibition as their possible endogenous mechanisms of action.

Made available in DSpace on 2020-12-12T02:32:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-05-14 A series of N-phenyl-2,5-dimethylpyrrole derivatives, designed as hybrids of the antitubercular agents BM212 and SQ109, have been synthesized and evaluated against susceptible and drug-resistant mycobacteria strains. Compound 5d, bearing a cyclohexylmethylene side chain, showed high potency against M. tuberculosis including MDR-TB strains at submicromolar concentrations. The new compound shows bacteriostatic activity and low toxicity and proved to be effective against intracellular mycobacteria too, showing an activity profile similar to isoniazid. School of Cancer and Pharmaceutical Sciences King's College London, 150 Stamford Street Dipartimento di Biotecnologie Chimica e Farmacia, via A. Moro 2 Tuberculosis Research Laboratory School of Pharmaceutical Sciences Sao Paulo State University (UNESP), Rod. Araraquara-Jau, km1 Centre for Clinical Microbiology University College London Mycobacteria Research Laboratory Department of Biological Sciences Institute of Structural and Molecular Biology Birkbeck University of London, Malet Street Department of Chemistry Faculty of Exact Sciences Bar-Ilan University Tuberculosis Research Laboratory School of Pharmaceutical Sciences Sao Paulo State University (UNESP), Rod. Araraquara-Jau, km1

Khesari dhal (Lathyrus sativus L) or grass pea is one of the richest source of protein among pulses, however its utilization is limited owing to the presence of a neurotoxin i.e. β-Oxalyl-di-amino propionic acid (β-ODAP). β-ODAP is a water soluble neurotoxin, hence, aqueous extraction of protein followed by isolation through precipitation may reduce/remove its concentration in protein isolates. . This study was aimed to optimize the process parameters for production of protein isolates from Khesari dhal (var. Mahateora). Four process parameters i. e extraction pH (8–10), extraction duration (40–80 min), extraction temperature (40–60 °C) and salt (sodium chloride) concentration (0.1–0.3%) were selected. Experiments were designed using response surface methodology (RSM) and executed accordingly. Maximum protein extraction (94.66%), recovery (81.04%), yield (23.10%) and purity (92.91%) was obtained at, pH 9; extraction duration, 58 min; temperature, 53 °C and salt concentration of 0.2% at khesari dhal: water ratio of 1:10. β-ODAP was not detectable in protein isolates and functional properties namely protein solubility, foaming and emulsification capacity, water and oil absorption capacity and least gelling concentration were at par with other legumes protein isolates.

In this study, quinoa protein isolate (QPI) (0, 4.0, 8.0 and 12.0 g/100 g) incorporated pasta was characterize concerning nutritional, physical, textural and morphological attributes. Supplementation of QPI from 0 to 12.0 g/100 g significantly (p

In connection with our research program on the development of novel anti-tubercular candidates, herein we report the design and synthesis of two different sets of indole-thiazolidinone conjugates (8a,b; 11a-d) and (14a-k; 15a-h). The target compounds were evaluated for their in vitro antibacterial and antifungal activities against selected human pathogens viz. Staphylococcus aureus (Gram positiveve), Pseudomonas aeruginosa, Escherichia coli (Gram negative), Mycobacterium tuberculosis (Acid-fast bacteria), Aspergillus fumigates and Candida albicans (fungi). Moreover, eukaryotic cell-toxicity was tested via an integrated ex vivo drug screening model in order to evaluate the selective therapeutic index (SI) towards antimicrobial activity when microbes are growing inside primary immune cells. Also, the cytotoxicity towards a panel of cancer cell lines and human lung fibroblast normal cell line, WI-38 cells, was explored to assure their safety. Compound 15b emerged as a hit in this study with potent broad spectrum antibacterial (MIC: 0.39–0.98 μg/mL) and antifungal (MIC: 0.49–0.98 μg/mL) activities, in addition to its ability to kill mycobacteria M. aurum inside an infected macrophage model with good therapeutic window. Moreover, compound 15b displayed promising activity towards resistant bacteria strains MRSA and VRE with MIC values equal 3.90 and 7.81 μg/mL, respectively. These results suggest compound 15b as a new therapeutic lead with good selectivity for further optimization and development.

Mycobacterium aurum (M. aurum) is an environmental mycobacteria that has previously been used in studies of anti-mycobacterial drugs due to its fast growth rate and low pathogenicity. The M. aurum genome has been sequenced and assembled into 46 contigs, with a total length of 6.02Mb containing 5684 annotated protein-coding genes. A phylogenetic analysis using whole genome alignments positioned M. aurum close to Mycobacterium vaccae and Mycobacterium vanbaalenii, within a clade related to fast-growing mycobacteria. Large-scale genomic rearrangements were identified by comparing the M. aurum genome to those of Mycobacterium tuberculosis and Mycobacterium leprae. M. aurum orthologous genes implicated in resistance to anti-tuberculosis drugs in M. tuberculosis were observed. The sequence identity at the DNA level varied from 68.6% for pncA (pyrazinamide drug-related) to 96.2% for rrs (streptomycin, capreomycin). We observed two homologous genes encoding the catalase-peroxidase enzyme (katG) that is associated with resistance to isoniazid. Similarly, two embB homologues were identified in the M. aurum genome. In addition to describing for the first time the genome of M. aurum, this work provides a resource to aid the use of M. aurum in studies to develop improved drugs for the pathogenic mycobacteria M. tuberculosis and M. leprae.

CONTEXT: Variations in the peritoneal reflections of the gallbladder are encountered during surgery and post-mortem examinations mainly form of mesentery and often have significant clinical implications, which can be life threatening at times. AIM: In this study, the manner of the peritoneal reflection over the gall bladder, its relative adherence to the gall bladder fossa and the relation of the fundus to the inferior margin of liver was examined. SETTINGS AND DESIGN: This cadaveric gross anatomical study was undertaken in the Department of Anatomy, Jawaharlal Nehru Medical College, Sawangi (Meghe), Wardha, Maharashtra, India and Subharti Medical College, Meerut, Uttar Pradesh, India, in the course a four year period i.e. 2008 to 2012, after obtaining necessary permission from the Institutional Ethical Committees. METHODS AND MATERIAL: It was carried out on one hundred gall bladders specimens, obtained from 10% formalin fixed cadavers during routine undergraduate students dissection The liver along with the gall bladder was retrieved from the abdominal cavity during undergraduate dissection of the abdomen and the peritoneal reflection over it was studied. RESULTS: Differential peritoneal reflections were observed in seven out of hundred specimens and formation of mesentery over the whole organ was found in two. In two there was mesentery over the neck and upper part of body. One the gall bladder was found floating in the gall bladder fossa but without the formation of mesentery. CONCLUSIONS: Differential peritoneal reflections of gall bladder were seen in seven specimens and mesentery formation to various degrees was seen in four. It was observed that peritoneal attachment of the gall bladder and the relative adherences of the viscus to the gall bladder fossa were closely associated.

5-Substituted-6-acetyl-2-amino-7-methyl-5,8-dihydropyrido[2,3-d]pyrimidin-4(3H)-one derivatives were synthesized and evaluated against Mycobacterium tuberculosis H37Rv, Mycobacterium aurum, Escherichia coli, and Staphylococcus aureus as well as a human monocyte-derived macrophage (THP-1), and murine macrophage (RAW 264.7) cell lines to assess their antibacterial and cytotoxic potential, respectively. The compounds showed activity in the range of 1.95-125 µg/ml against M. tuberculosis but showed no activity against M. aurum, E. coli, and S. aureus, indicating selectivity towards slow-growing mycobacterial pathogens. The compounds exhibited very low to no cytotoxicity up to 500 µg/ml concentration against eukaryotic cell lines. The most potent molecule, 2l, showed a minimum inhibitory concentration of 1.95 µg/ml against M. tuberculosis H37Rv and a selectivity index of >250 against both the eukaryotic cell lines. Furthermore, 2l showed moderate inhibition of whole-cell mycobacterial drug-efflux pumps when compared to verapamil, a known potent inhibitor of efflux pumps. Thus, derivative 2l was identified as an antituberculosis hit molecule, which could be used to yield more potent lead molecules.

Objectives The intracellularly surviving and slow-growing pathogen, Mycobacterium tuberculosis, adapts the host cell environment for its active and dormant life cycle. It is evident that the lack of appropriate high-throughput screening of inhibitors within host cells is an impediment for the early stages of anti-tubercular drug discovery. We aimed to develop an integrated surrogate model that enhances the screening of large inhibitor libraries. Methods Different mycobacterial species were compared for their growth, drug susceptibility and intracellular uptake. A 6-well plate solid agar-based spot culture growth inhibition (SPOTi) assay was developed into a higher throughput format. The uptake and intracellular survival of Mycobacterium aurum within mouse macrophage cells (RAW 264.7) were optimized using 24/96-well plate formats. Results Fast-growing, non-pathogenic M. aurum was found to have an antibiotic-susceptibility profile similar to that of M. tuberculosis. The sensitivity to an acidic pH environment and the ability to multiply inside RAW 264.7 macrophages provided additional advantages for employing M. aurum in intracellular drug screening methods. A selection of anti-tubercular drugs inhibited the growth and viability of M. aurum inside the macrophages at different levels. Conclusions We present a rapid, convenient, high-throughput surrogate model, which provides a comprehensive evaluation platform for new chemical scaffolds against different physiological stages of mycobacteria within the primary cell environment of the host. The results using anti-tubercular drugs validate this model for screening libraries of existing and novel chemical entities.

One-third of the global human population harbours Mycobacterium tuberculosis in dormant form. This dormant or latent infection presents a major challenge for global efforts to eradicate tuberculosis, because it is a vast reservoir of potential reactivation and transmission. This article explains how the pathogen evades the host immune response to establish a latent infection, and how it emerges from a state of latency to cause reactivation disease. This review highlights the key factors responsible for immune evasion and reactivation. It concludes by identifying interesting candidates for drug or vaccine development, as well as identifying unresolved questions for the future research.

Objectives The aim of this study was to comprehensively evaluate the antibacterial activity and MurE inhibition of a set of N-methyl-2-alkenyl-4-quinolones found to inhibit the growth of fast-growing mycobacteria. Methods Using the spot culture growth inhibition assay, MICs were determined for Mycobacterium tuberculosis H37Rv, Mycobacterium bovis BCG and Mycobacterium smegmatis mc2155. MICs were determined for Mycobacterium fortuitum, Mycobacterium phlei, methicillin-resistant Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa using microplate dilution assays. Inhibition of M. tuberculosis MurE ligase activity was determined both by colorimetric and HPLC methods. Computational modelling and binding prediction of the quinolones in the MurE structure was performed using Glide. Kinetic experiments were conducted for understanding possible competitive relations of the quinolones with the endogenous substrates of MurE ligase. Results The novel synthetic N-methyl-2-alkenyl-4-quinolones were found to be growth inhibitors of M. tuberculosis and rapid-growing mycobacteria as well as methicillin-resistant S. aureus, while showing no inhibition for E. coli and P. aeruginosa. The quinolones were found to be inhibitory to MurE ligase of M. tuberculosis in the micromolar range (IC50 ∼40–200 μM) when assayed either spectroscopically or by HPLC. Computational docking of the quinolones on the published M. tuberculosis MurE crystal structure suggested that the uracil recognition site is a probable binding site for the quinolones. Conclusions N-methyl-2-alkenyl-4-quinolones are inhibitors of mycobacterial and staphylococcal growth, and show MurE ligase inhibition. Therefore, they are considered as a starting point for the development of increased affinity MurE activity disruptors.

A novel alkylated unsaturated p-benzoquinone designated as 3-[(z)-12'-heptadecenyl]-2-hydroxy-5-methoxy-1,4-benzoquinone was isolated from hexane extract of the rhizomes of Iris kumaonensis and it's structure was confirmed by extensive spectroscopic analysis, IR, MS, HREIMS, 1D, 2D NMR and comparison with the literature data of known compounds.

Objective: The study was conducted to know the prevalence of cervical rib in Indian population especially in and around Lucknow and to compare the results with the other study reported in London population. Material and Method: The study was conducted on chest X-rays of 12950 cases done for various complaints of both male and female patients, irrespective of age and ethnicity who attended the Radiology Department of Era's Lucknow Medical College, Lucknow during a period of 7 months, that is from 01-09-2011 to 31-03-2012. Results: An incidence of 0.6% was observed with bilateral cervical rib being more common in both males and females and the incidence of cervical rib in females was 0.73% as compared to 0.49% in males. Conclusion: Indian population showed an overall incidence of 0.6% as compared to the London population showing an overall incidence of 0.74%. Bilateral cervical rib is more common in both male and females and left sided cervical rib being more common in males in comparison to right sided cervical rib in females.

Objectives: Lead antituberculosis (anti-TB) molecules with novel mechanisms of action are urgently required to fuel the anti-TB drug discovery pipeline. The aim of this study was to validate the use of the high-throughput spot culture growth inhibition (HT-SPOTi) assay for screening libraries of compounds against Mycobacterium tuberculosis and to study the inhibitory effect of ibuprofen (IBP) and the other 2-arylpropanoic acids on the growth inhibition of M tuberculosis and other mycobacterial species.\ud \ud Methods: The HT-SPOTi method was validated not only with known drugs but also with a library of 47 confirmed anti-TB active compounds published in the ChEMBL database. Three over-the-counter non-steroidal anti-inflammatory drugs were also included in the screening. The 2-arylpropanoic acids, including IBP, were comprehensively evaluated against phenotypically and physiologically different strains of mycobacteria, and their cytotoxicity was determined against murine RAW264.7 macrophages. Furthermore, a comparative bioinformatic analysis was employed to propose a potential mycobacterial target.\ud \ud Results: IBP showed antitubercular properties while carprofen was the most potent among the 2-arylpropanoic class. A 3,5-dinitro-IBP derivative was found to be more potent than IBP but equally selective. Other synthetic derivatives of IBP were less active, and the free carboxylic acid of IBP seems to be essential for its anti-TB activity. IBP, carprofen and the 3,5-dinitro-IBP derivative exhibited activity against multidrug-resistant isolates and stationary phase bacilli. On the basis of the human targets of the 2-arylpropanoic analgesics, the protein initiation factor infB (Rv2839c) of M tuberculosis was proposed as a potential molecular target.\ud \ud Conclusions: The HT-SPOTi method can be employed reliably and reproducibly to screen the antimicrobial potency of different compounds. IBP demonstrated specific antitubercular activity, while carprofen was the most selective agent among the 2-arylpropanoic class. Activity against stationary phase bacilli and multidrug-resistant isolates permits us to speculate a novel mechanism of antimycobacterial action. Further medicinal chemistry and target elucidation studies could potentially lead to new therapies against TB.

© 2013 Munshi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ATP-dependent Mur ligases (Mur synthetases) play essential roles in the biosynthesis of cell wall peptidoglycan (PG) as they catalyze the ligation of key amino acid residues to the stem peptide at the expense of ATP hydrolysis, thus representing potential targets for antibacterial drug discovery. In this study we characterized the division/cell wall (dcw) operon and identified a promoter driving the co-transcription of mur synthetases along with key cell division genes such as ftsQ and ftsW. Furthermore, we have extended our previous investigations of MurE to MurC, MurD and MurF synthetases from Mycobacterium tuberculosis. Functional analyses of the pure recombinant enzymes revealed that the presence of divalent cations is an absolute requirement for their activities. We also observed that higher concentrations of ATP and UDP-sugar substrates were inhibitory for the activities of all Mur synthetases suggesting stringent control of the cytoplasmic steps of the peptidoglycan biosynthetic pathway. In line with the previous findings on the regulation of mycobacterial MurD and corynebacterial MurC synthetases via phosphorylation, we found that all of the Mur synthetases interacted with the Ser/Thr protein kinases, PknA and PknB. In addition, we critically analyzed the interaction network of all of the Mur synthetases with proteins involved in cell division and cell wall PG biosynthesis to re-evaluate the importance of these key enzymes as novel therapeutic targets in anti-tubercular drug discovery. © 2013 Munshi et al. Medical Research Council, UK (www.mrc.ac.uk). Investigators Research Grant award to SB (Grant Code: G0801956)

The n-hexane extract of Lovage root was found to significantly inhibit the growth of both Mycobacterium smegmatis mc2155 and Mycobacterium bovis BCG, and therefore a bioassay-guided isolation strategy was undertaken. (Z)-Ligustilide, (Z)-3-butylidenephthalide, (E)-3-butylidenephthalide, 3-butylphthalide, α-prethapsenol, falcarindiol, levistolide A, psoralen and bergapten were isolated by chromatographic techniques, characterized by NMR spectroscopy and MS, and evaluated for their growth inhibition activity against Mycobacterium tuberculosis H37Rv using the whole-cell phenotypic spot culture growth inhibition assay (SPOTi). Cytotoxicity against RAW 264.7 murine macrophage cells was employed for assessing their degree of selectivity. Falcarindiol was the most potent compound with a minimum inhibitory concentration (MIC) value of 20 mg/L against the virulent H37Rv strain; however, it was found to be cytotoxic with a half-growth inhibitory concentration (GIC50) in the same order of magnitude (SI

In a project to characterise new antibacterial chemotypes from plants, hyperenone A and hypercalin B were isolated from the hexane and chloroform extracts of the aerial parts of Hypericum acmosepalum. The structures of both compounds were characterised by extensive one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and were confirmed by mass spectrometry. Hyperenone A and hypercalin B exhibited antibacterial activity against multidrug-resistant strains of Staphylococcus aureus, with minimum inhibition concentration ranges of 2–128mg/L and 0.5–128mg/L, respectively. Hyperenone A also showed growth-inhibitory activity against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG at 75mg/L and 100mg/L. Neither hyperenone A nor hypercalin B inhibited the growth of Escherichia coli and both were non-toxic to cultured mammalian macrophage cells. Both compounds were tested for their ability to inhibit the ATP-dependent MurE ligase of M. tuberculosis, a crucial enzyme in the cytoplasmic steps of peptidoglycan biosynthesis. Hyperenone A inhibited MurE selectively, whereas hypercalin B did not have any effect on enzyme activity.