Design of 1-(furan-2-yl)-N-(5-substituted phenyl-1, 3, 4-thiadiazol-2-yl) methanimine derivatives as Enoyl-ACP reductase inhibitors: Synthesis, molecular docking studies and antitubercular activity

A series of 5-phenylsubstiuted 1, 3, 4 thiadiazoles clubbed with furan moiety (Fa-Fe) by means of azomethine linkage have been synthesized. All the newly synthesized compounds were characterized by IR,1HNMR and Mass analyses. All the synthesized molecules have been predicted as antitubercular in nature by PASS in silico approach. In vitro antitubercular screening was performed by alamar blue assay method on Mycobacterium tuberculosis H37Rv strain. Among the synthesized derivatives Fb and Fe were active at 3.125 µg/mL against M. tuberculosis H37Rv strain. The mechanism of action of the active compounds was carried out by docking of receptor enoyl-ACP reductase. It has been concluded that both Fb and Fe posses a significant interaction of hydrogen bonding and electrostatic attraction with Tyr 158 and Met103 in the active site of enzyme

Community Investment in the Digital Divide Pays Dividends for Years to Come

As the COVID-19 pandemic has led to unprecedented trials experienced by almost every population in the way of public health, food systems, businesses and families, Information and Communication Technologies (ICT) have helped to mitigate many challenges. The hope of the many academic research efforts taken during this time will help those in civic authority understand these impacts as civic leaders make decisions about the areas of society and the community that need emergency funds and how to allocate future expenditures to best serve the populations within the community. At-risk populations that have limited or no access to the Internet / ICT or who lack the skills to effectively use it can fall into a state of social isolation which prior research has shown can have costly health implications such as an increase in cardiac disease, diabetes and liver disease which is due to lack of exercise and depression brought on by the isolation. An investment in ICT now will strengthen communities and families. This research in progress paper investigates the barriers to getting ICT to at-risk populations and the present and future costs to society for failing to do so. Finally, several implications will be extracted, particularly those that will become part of a Strategic Framework that can be implemented in every city across the United States to pinpoint at-risk populations and define the best remedies per demographic to bridge the digital divide so that every population is connected to their caregiver network and the latest health information

Development of novel (1-H) benzimidazole bearing pyrimidine-trione based MAO-A inhibitors: Synthesis, docking studies and antidepressant activity

The synthesis of some novel (1-H) benzimidazole bearing pyrimidine-trione based MAO-A inhibitors were achieved by the reaction between 2E)-1-(1H-benzimidazol-2-yl)-3-phenylprop-2-en-1-ones(4a–f) and barbituric acid in the presence of a catalytic amount of acetic acid medium. All the final structures were assigned on the basis of IR, 1HNMR and mass spectra analyses. All the synthesized derivatives showed good antidepressant activity when compared to the standard clomipiramine at a dose level of 20 mg/kg. The compound (5d) 5-{(2E)-1-(1H-benzimidazol-2-yl)-3-[4-(dimethylamino)phenyl] prop-2-en-1-ylidene} pyrimidine-2, 4, 6(1H,3H,5H)-trione significantly reduced the duration of immobility times at 50 mg/kg−1 dose level when compared to the standard drug. Molecular docking studies revealed the need for an extra hydrophobic interaction in the titled scaffold for acquiring the promising experimental values. It has been concluded that the computational values obtained after the docking calculation are in good agreement with the experimental values

Chalcones: Unearthing their therapeutic possibility as monoamine oxidase B inhibitors

In the last years the continuous efforts in the development of novel and effective inhibitors of human monoamine oxidases (hMAOs) promoted the discovery of new agents able to effectively and selectively bound one of the two isoforms (hMAO-A and hMAO-B). However, the parent chalcone scaffold still covers an important role in hMAOs inhibition. In the present work, we focused our attention on the researches performed in the last five years, involving chalcones or compounds that can be correlated to them. We classified the chalcones into different groups depending on their structural characteristics or common molecular properties. In this regard, we also considered chalcones based on heterocycles and compounds endowed with scaffolds containing a masked chalcone motif. When structural attributes could not be used, we took advantage of enzymatic activity to arrange compounds in a group. We followed this approach for the multitarget agents. Finally, we also analysed the naturally occurring chalcones. All the sections were discussed exhaustively and the structure-activity relationship (SAR) analyses were sustained by means of detailed images describing the effects related to the substituents or structural changes

Discovery of some novel imines of 2-amino, 5-thio, 1,3,4-thiadiazole as mucomembranous protector. Synthesis, anti-oxidant activity and in silico PASS approach

A series of some novel imines (6a–f) of 2-amino, 5-thio 1,3,4-thiadiazole connected to benzimidazole chalcones were prepared. The structures of the final imines were ascertained by IR, 1HNMR, mass and elemental analyses. Predicted activity spectra of all the final derivatives were determined in the category of mucomembranous protector nature with a Pa value more than 0.7. All the newly synthesized compounds were screened for their antiulcer activity in the pylorus-ligated rats. Free radical scavenging activity of all final derivatives was determined by DPPH method.Compounds 6e, 6a and 6b showed a percentage protection of (73.47, 72.17 and 70.43 at a dose of 10mg/kgb.w.) when compared to standard omeprazole (77.37%, 2mg/kgb.w.). Compounds 6e, 6a and 6b showed free radical scavenging activity with an IC50 of 0.32, 0.39 and 0.49mM respectively. Scanning of stomach specimens using electron microscope revealed that the mice treated with standard and synthetic derivatives had no injury observed in stomach mucosa, which is identical to that of the control animal. It has been concluded that ulcer healing properties of the imines are probably due to their antioxidant action

Determination of in vitro free radical scavenging and antiproliferative effect of Pennisetum alopecuroides on cultured A549 human lung cancer cells

Context: Pennisetum alopecuroides (Poaceae) is a grass predominantly distributed in tropics and sub tropics. It is used as a cattle feed in many regions. Aim: The objective of the present study was to investigate the in vitro free radical scavenging and antiproliferative activity of ethanol extract of P. alopecuroides (EEPA) on cultured A549 human lung cancer cell lines. Settings and Design: The anti-oxidant activity of ethanol extract was evaluated at dose level 12.5, 25, 50, 100, and 200 μg/ml. The in vitro antiproliferative activity was measured at doses of 10, 50, and 100 μg/ml. Materials and Methods: The free radical scavenging activity of the EEPA was determined by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) method and in vitro antiproliferative activity on A549 human lung cancer cells was conducted by using MTT assay method. Results: The phytochemical screening revealed that the P. alopecuroides contained alkaloids, tannins, saponins, and flavonoids as the major secondary metabolites. The IC 50 value of DPPH scavenging activity was found to be 44.41 μg/ml and 31.02 μg/ml  for a mixture of EEPA and standard ascorbic acid, respectively. In vitro MTT assay showed that EEPA had anti-proliferation effects on A549 cells in a dose dependent manner. Conclusions: This is the 1 st time a pharmacological exploration of P. alopecuroides grasses has been conducted. We have shown that P. alopecuroides exhibits good free radical scavenging and strong in vitro cytotoxic activities against human lung cancer cell lines

Emerging Signal Regulating Potential of Small Molecule Biflavonoids to Combat Neuropathological Insults of Alzheimer Disease

International audienceAlzheimer's disease (AD) is a progressive, chronic and severe neurodegenerative disorder which is linked with cognitive and memory impairment eventually can even lead to death. There are several processes which can cause AD, including mitochondrial dysfunction-mediated oxidative stress (OS), intracellular buildup of hyper-phosphorylated tau as neurofibrillary tangles (NFTs) and excessive buildup of extracellular amyloid beta (Aβ) plaques, and/or genetic as well as the environmental factors. Existing treatments can only provide symptomatic relief via providing temporary palliative therapy which can weaken the rate of AD-associated cognitive decline. Plants are the fundamental building blocks for the environment and produce various secondary metabolites. Biflavonoids are one among such secondary metabolite that possesses the potential to mediate noticeable change in the aggregation of Aβ and also efficiently can decrease the toxic effects of Aβ oligomers in comparison with the monoflavonoid moieties. Nevertheless, the molecular processes are yet to be well explained. However, flavonoids are found to cause a change in the Aβ and tau aggregation pathway to generate non-toxic aggregates. In this review, we have discussed the neuroprotective action of small molecule biflavonoid to reduce the neurodegenerative events of AD. Furthermore, this appraisal advances our knowledge to develop potential new targets for the treatment of AD

Design of 1-(furan-2-yl)-N-(5-substituted phenyl-1, 3, 4-thiadiazol-2-yl) methanimine derivatives as Enoyl-ACP reductase inhibitors: Synthesis, molecular docking studies and anti-tubercular activity

A series of 5-phenylsubstiuted 1, 3, 4 thiadiazoles clubbed with furan moiety (Fa-Fe) by means of azomethine linkage have been synthesized. All the newly synthesized compounds were characterized by IR,1HNMR and Mass analyses. All the synthesized molecules have been predicted as anti-tubercular in nature by PASS in silico approach. In vitro anti-tubercular screening was performed by alamar blue assay method on Mycobacterium tuberculosis H37Rv strain. Among the synthesized derivatives Fb and Fe were active at 3.125 µg/mL against Mycobacterium tuberculosis H37Rv strain. The mechanism of action of the active compounds was carried out by docking of receptor enoyl-ACP reductase. It has been concluded that both Fb and Fe posses a significant interaction of hydrogen bonding and electrostatic attraction with Tyr 158 and Met103 in the active site of enzyme