Discovery of aminopiperidine based potent & novel topoisomerase inhibitor with broad spectrum anti-bacterial activity.

Bacterial DNA gyrase and topoisomerase IV inhibition has emerged as a promising strategy for the cure of infections caused by antibiotic-resistant bacteria. The Novel Bacterial Topoisomerase Inhibitors (NBTIs) bind to a different site from that of the quinolones with novel mechanism of action. This evades the existing target-mediated bacterial resistance associated with quinolones.

Synergistic effect of nickel and temperature on gene expression, multiple stress markers, and depuration: an acute toxicity in fish.

Aquatic animals are prone to extinction due to metal pollution and global climate change. Even though the fish and their products are also unsafe for human consumption, their exports have been rejected due to inorganic and organic contaminants. Nickel (Ni) is a metal that induces toxicity and accumulates in the aquatic ecosystem, posing health threats to humans, animals, and fish.

Protective role of selenium and selenium-nanoparticles against multiple stresses in Pangasianodon hypophthalmus.

Pollution and climate change pose significant threats to aquatic ecosystems, with adverse impacts on aquatic animals, including fish. Climate change increases the toxicity of metal in aquatic ecosystems. To understand the severity of metal pollution and climate change, an experiment was conducted to delineate the mitigation potential of selenium (Se) and selenium nanoparticles (Se-NPs) against lead (Pb) and high temperature stress in Pangasianodon hypophthalmus.

Nano‑zinc enhances gene regulation of non‑specific immunity and antioxidative status to mitigate multiple stresses in fish.

The toxicity of ammonia surged with arsenic pollution and high temperature (34 °C). As climate change enhances the pollution in water bodies, however, the aquatic animals are drastically affected and extinct from nature. The present investigation aims to mitigate arsenic and ammonia toxicity and high-temperature stress (As + NH + T) using zinc nanoparticles (Zn-NPs) in Pangasianodon hypophthalmus.

Nano-copper Enhances Gene Regulation of Non-specific Immunity and Antioxidative Status of Fish Reared Under Multiple Stresses.

Arsenic pollution, water temperature, and pH are the major concern for aquaculture. Moreover, the aim of the present investigation was to delineate the role of nano-copper (Cu-NPs) in the mitigation of arsenic toxicity, high temperature (34 °C) and low pH (6.5) stress on Pangasianodon hypophthalmus.

Exploring mitigating role of zinc nanoparticles on arsenic, ammonia and temperature stress using molecular signature in fish.

Background: The pollution and climate change in aquatic ecosystems are major problems threatening the aquatic organisms for existence in the recent timeline, which promotes the extinction of the fish species. However, the present study dealt with zinc nanoparticles (Zn-NPs) in mitigating arsenic, ammonia and high temperature stresses in Pangasianodon hypophthalmus.

Materials And Methods: To studying different gene expressions, an experiment was conducted to mitigate the multiple stressors using dietary Zn-NPs at 0, 2, 4, and 6 mg kg diets.

Selenium nanoparticles and omega-3 fatty acid enhanced thermal tolerance in fish against arsenic and high temperature.

The aquatic ecosystem is prone to global climate change and pollution affecting aquatic animals, including fish. In light of the above, we experimented with delineate the role of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with selenium nanoparticles (Se-NPs) to enhance the thermal tolerance in Pangasianodon hypophthalmus reared under control or concurrent exposure to high temperature and arsenic (As + T) for 112 days. Se-NPs were synthesized using the green approach.

Multi-biomarker approach to assess chromium, pH and temperature toxicity in fish.

Chromium (Cr) is considered as the most common ubiquitous pollutant for aquatic animals including fish. An experiment was conducted to determine the acute and chronic toxicity of Cr, pH and high temperature in Anabas testudineus. Lethal concentration (LC) of Cr alone was determined as 55.

Discovery of novel, potent and orally efficacious inhibitor of neutral amino acid transporter BAT1 (SLC6A19).

Amino acid restriction by inhibition of neutral amino acid transporter, BAT1 (SLC6A19) activity has been recently shown to improve glyceamic control by upregulating glucagon like peptide (GLP1) and fibroblast growth factor (FGF21) in mice. Hence, pharmacological inhibition of BAT1 is expected to treat type-2 diabetes and related disorder. In this study, rationally designed trifluoromethyl sulfonyl derivatives were identified as novel, potent and orally bioavailable BAT1 inhibitors.

Discovery of diaminopyrimidine-carboxamide derivatives as JAK3 inhibitors.

Selective inhibition of janus kinase (JAK) has been identified as an important strategy for the treatment of autoimmune disorders. Optimization at the C2 and C4-positions of pyrimidine ring of Cerdulatinib led to the discovery of a potent and orally bioavailable 2,4-diaminopyrimidine-5-carboxamide based JAK3 selective inhibitor (11i). A cellular selectivity study further confirmed that 11i preferentially inhibits JAK3 over JAK1, in JAK/STAT signaling pathway.

Revisiting glitazars: thiophene substituted oxazole containing α-ethoxy phenylpropanoic acid derivatives as highly potent PPARα/γ dual agonists devoid of adverse effects in rodents.

In an effort to develop safe and efficacious compounds for the treatment of metabolic disorders, novel thiophene substituted oxazole containing α-alkoxy-phenylpropanoic acid derivatives are designed as highly potent PPARα/γ dual agonists. These compounds were found to be efficacious at picomolar concentrations. Lead compound 18d has emerged as very potent PPARα/γ dual agonist demonstrating potent antidiabetic and lipid lowering activity at a very low dose and did not exhibit any significant signs of toxicity in rodents.

Diaryl dihydropyrazole-3-carboxamides with significant in vivo antiobesity activity related to CB1 receptor antagonism: synthesis, biological evaluation, and molecular modeling in the homology model.

A number of analogues of diaryl dihydropyrazole-3-carboxamides have been synthesized. Their activities were evaluated for appetite suppression and body weight reduction in animal models. Depending on the chemical modification of the selected dihydropyrazole scaffold, the lead compounds--the bisulfate salt of (+/-)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 26 and the bisulfate salt of (-)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 30--showed significant body weight reduction in vivo, which is attributed to their CB1 antagonistic activity and exhibited a favorable pharmacokinetic profile.