Discovery, SAR and mechanistic studies of quinazolinone-based acetamide derivatives in experimental visceral leishmaniasis.

Towards identification of novel therapeutic candidates, a series of quinazolinone-based acetamide derivatives were synthesized and assessed for their anti-leishmanial efficacy. Amongst synthesized derivatives, compounds F12, F27 and F30 demonstrated remarkable activity towards intracellular L. donovani amastigotes in vitro, with IC50 values of 5.76 ± 0.84 µM, 3.39 ± 0.85 µM and 8.26 ± 1.23 µM against promastigotes, and 6.02 µM ± 0.52, 3.55 ± 0.22 µM and 6.23 ± 0.13 µM against amastigotes, respectively. Oral administration of compounds F12 and F27 entailed >85% reduction in organ parasite burden in L. donovani-infected BALB/c mice and hamsters, by promoting host-protective Th1 cytokine response. In host J774 macrophages, mechanistic studies revealed inhibition of PI3K/Akt/CREB axis, resulting in a decrease of IL-10 versus IL-12 release upon F27 treatment. In silico docking studies conducted with lead compound, F27 demonstrated plausible inhibition of Leishmania prolyl-tRNA synthetase, which was validated via detection of decreased proline levels in parasites and induction of amino acid starvation, leading to G1 cell cycle arrest and autophagy-mediated programmed cell death of L. donovani promastigotes. Structure-activity analysis and study of pharmacokinetic and physicochemical parameters suggest oral availability and underscore F27 as a promising lead for anti-leishmanial drug development.

Mechanistic Concept of Physiological, Biochemical, and Molecular Responses of the Potato Crop to Heat and Drought Stress.

Most cultivated potatoes are tetraploid, and the tuber is the main economic part that is consumed due to its calorific and nutritional values. Recent trends in climate change led to the frequent occurrence of heat and drought stress in major potato-growing regions worldwide. The optimum temperature for tuber production is 15-20 °C. High-temperature and water-deficient conditions during the growing season result in several morphological, physiological, biochemical, and molecular alterations. The morphological changes under stress conditions may affect the process of stolon formation, tuberization, and bulking, ultimately affecting the tuber yield. This condition also affects the physiological responses, including an imbalance in the allocation of photoassimilates, respiration, water use efficiency, transpiration, carbon partitioning, and the source-sink relationship. The biochemical responses under stress conditions involve maintaining ionic homeostasis, synthesizing heat shock proteins, achieving osmolyte balance, and generating reactive oxygen species, ultimately affecting various biochemical pathways. Different networks that include both gene regulation and transcription factors are involved at the molecular level due to the combination of hot and water-deficient conditions. This article attempts to present an integrative content of physio-biochemical and molecular responses under the combined effects of heat and drought, prominent factors in climate change. Taking into account all of these aspects and responses, there is an immediate need for comprehensive screening of germplasm and the application of appropriate approaches and tactics to produce potato cultivars that perform well under drought and in heat-affected areas.

Status of pulse milling processes and technologies: A review.

Pulses are essential component of the human diet in the underdeveloped and the developing countries. Pulse milling mainly focuses on complete removal of the hull with minimum generation of powder, broken, and in certain cases dehulled split formation. Physical and mechanical properties of different pulses are described and their role in dehulling is discussed in this review. The review discusses nature of gums that binds hull and cotyledons together and their effect on milling characteristics. Pitting operation is performed for all pulses prior to the pretreatment for better dehulling. Various pretreatment processes (soaking, edible oils, chemicals, enzymes, hydrothermal) developed to loosen the bond are examined for their dehulling efficacy from commercial application viewpoint. Dependence of dehulling characteristics of different pulses on size, shape, variety, grain hardness, and moisture content are discussed. Most of the machines developed for pulses dehulling in India are abrasion based emery-cylinder concave system. The studies done for optimization of different pretreatment process conditions are also reviewed. The losses taking place in the form of broken and powder during pulse milling are described. Methods for performance evaluation of the pulse dehulling system are reviewed and expressions are suggested for proper evaluation. This review gives complete overview of the processes and technological status of pulse milling in present context.

Development of protein fortified mango based ready-to-serve beverage.

Fruit drinks contain negligible amount of protein as nutritional component. Fortification of fruit drinks with protein is a challenge due to protein stability in acidic and ionic environment. Mango ready-to-serve (RTS) beverage was fortified with modified whey protein and its rheological properties were studied. Whey protein was hydrolysed with papain to improve its stability in acidic medium. The water holding capacity of whey protein increased about two times after hydrolysis. Hydrolysed and native whey protein was used at 2, 3 and 4% levels for fortification of mango based RTS beverage. Addition of hydrolysed whey protein at all the three levels did not significantly change the flow behaviour of the beverage. Native whey protein fortification resulted in precipitation; however, addition of hydrolysed whey protein led to stable beverage formulation at all the three levels. Hydrolysed whey protein imparted slight bitter taste to the RTS beverage, which was masked by ß-cyclodextrin @ 0.15% of total protein. The mango RTS beverage with 3.0% hydrolysed whey protein was found acceptable with good sensory appeal and stability during thermal processing as well storage in glass bottles.

Iron (II)-chelating activity of buffalo αS-casein hydrolysed by corolase PP, alcalase and flavourzyme.

Iron is a vital substance for human health which participates in many biochemical reactions. It also act as initiator for many harmful oxidative process. Buffalo αS-casein enriched fraction (80 %) was hydrolysed independently by corolase PP (H1), alcalase (H2), flavourzyme (H3) and sequentially by alcalase-flavourzyme (H4). After ultrafiltration (10 and 3 kDa) hydrolysates were analysed for their iron chelation activity using ferrozine. For H1 group of hydrolysates highest iron (II)-chelation activity (265.58 µM Fe(2+/)mg protein) was found after 8 h of hydrolysis for H2 (267.56 µM Fe(2+/)mg protein) and H3 group of hydrolysates (380.68 µM Fe(2+/)mg protein) after 6 h of hydrolysis. Sequential hydrolysis was not effective for iron (II)-chelation activity. 3 kDa fractions show higher iron (II)-chelation activity than 10 kDa fraction. Flavourzyme was more effective for generation of iron (II)-chelating peptides from buffalo αS-casein.