Mild, Aqueous α-Arylation of Ketones: Towards New Diversification Tools for Halogenated Metabolites and Drug Molecules

The COVID-19 pandemic has been responsible for several deaths worldwide. The causative agent behind this disease is the Severe Acute Respiratory Syndrome – novel Coronavirus 2 (SARS-nCoV2). SARS-nCoV2 belongs to the category of RNA viruses. The main protease, responsible for the cleavage of the viral polyprotein is considered as one of the hot targets for treating COVID-19. Earlier reports suggest the use of HIV anti-viral drugs for targeting the main protease of SARS-CoV, which caused SARS in the year 2002-03. Hence, drug repurposing approach may prove to be useful in targeting the main protease of SARS-nCoV2. The high-resolution crystal structure of 3CLpro (main protease) of SARS-nCoV2 (PDB ID: 6LU7) was used as the target. The Food and Drug Administration (FDA) approved and SWEETLEAD database of drug molecules were screened. The apo form of the main protease was simulated for a cumulative of 150 ns and 10 μs open source simulation data was used, to obtain conformations for ensemble docking. The representative structures for docking were selected using RMSD-based clustering and Markov State Modeling analysis. This ensemble docking approach for main protease helped in exploring the conformational variation in the drug binding site of the main protease leading to efficient binding of more relevant drug molecules. The drugs obtained as best hits from the ensemble docking possessed anti-bacterial and anti-viral properties. Small molecules with these properties may prove to be useful to treat symptoms exhibited in COVID-19. This in-silico ensemble docking approach would support identification of potential candidates for repurposing against COVID-19.

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Faculty Opinions recommendation of Impact of dendrimers on solubility of hydrophobic drug molecules.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727675143.793532929 ◽

2017 ◽

Author(s):

Donald A Tomalia

Keyword(s):

Hydrophobic Drug ◽

Drug Molecules

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Bioenhancing Effect of Cow Urine Distillate and Pepper Extract on Antibacterial Activity of Azadirachta Indica Leaves

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2016.9.2.8 ◽

1970 ◽

Vol 9 (2) ◽

pp. 3212-3214

Author(s):

Pramod Dhakal ◽

Ankit a Achary ◽

Vedamurthy Joshi

Keyword(s):

Antibacterial Activity ◽

Azadirachta Indica ◽

Pathogenic Bacteria ◽

Ethanol Extract ◽

Watery Diarrhea ◽

Diffusion Method ◽

E Coli ◽

Drug Molecules ◽

Cow Urine

Bioenhancers are drug facilitator which do not show the typical drug activity but in combination to enhance the activity of other molecule in several way including increase the bioavailability of drug across the membrane, potentiating the drug molecules by conformational interaction, acting as receptor for drug molecules and making target cell more receptive to drugs and promote and increase the bioactivity or bioavailability or the uptake of drugs in combination therapy. The objective of the present study was to evaluate the antibacterial and activity of combination in Azadirachta indica extract with cow urine distillate and pepper extract against common pathogenic bacteria, a causative agent of watery diarrhea. It has been found that Indian indigenous cow urine and its distillate also possess bioenhancing ability. Bioenhancing role of cow urine distillate (CUD) and pepper extract was investigated on antibacterial activity of ethanol extract of Azadirachta indica. Antibacterial activity of ethanol extract neem alone and in combination with CUD and pepper extract were determined the ATCC strains against Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and E-coli by cup plate diffusion method. Ethanol extract of neem has showed more effect on P. aeruginosa, E-coli than S. aureus and K. pneumonia with combination of CUD and pepper extract. CUD and pepper did not show any inhibition of test bacteria in low concentration. The antibacterial effect of combination of extract and CUD was higher than the inhibition caused by extract alone and is suggestive of the bioenhancing role of cow urine distillate and pepper. Moreover, inhibition of test bacteria was observed with less concentration of extract on combining with CUD

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Revalorizing Lignocellulose for the Production of Natural Pharmaceuticals and Other High Value Bioproducts

Current Medicinal Chemistry ◽

10.2174/0929867324666170912095755 ◽

2019 ◽

Vol 26 (14) ◽

pp. 2475-2484 ◽

Cited By ~ 4

Author(s):

Congqiang Zhang ◽

Heng-Phon Too

Keyword(s):

Clostridium Thermocellum ◽

White Rot Fungi ◽

Brown Rot ◽

Cost Effective ◽

White Rot ◽

Chemical Pretreatment ◽

Significant Challenge ◽

Drug Molecules ◽

Natural Medicine ◽

Renewable Natural Resource

Lignocellulose is the most abundant renewable natural resource on earth and has been successfully used for the production of biofuels. A significant challenge is to develop cost-effective, environmentally friendly and efficient processes for the conversion of lignocellulose materials into suitable substrates for biotransformation. A number of approaches have been explored to convert lignocellulose into sugars, e.g. combining chemical pretreatment and enzymatic hydrolysis. In nature, there are organisms that can transform the complex lignocellulose efficiently, such as wood-degrading fungi (brown rot and white rot fungi), bacteria (e.g. Clostridium thermocellum), arthropods (e.g. termite) and certain animals (e.g. ruminant). Here, we highlight recent case studies of the natural degraders and the mechanisms involved, providing new utilities in biotechnology. The sugars produced from such biotransformations can be used in metabolic engineering and synthetic biology for the complete biosynthesis of natural medicine. The unique opportunities in using lignocellulose directly to produce natural drug molecules with either using mushroom and/or ‘industrial workhorse’ organisms (Escherichia coli and Saccharomyces cerevisiae) will be discussed.

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Current Nanotechnological Approaches for an Effective Delivery of Bioactive Drug Molecules to Overcome Drug Resistance Tuberculosis

Current Pharmaceutical Design ◽

10.2174/1381612821666150531163254 ◽

2015 ◽

Vol 21 (22) ◽

pp. 3076-3089 ◽

Cited By ~ 12

Author(s):

Tarun Garg ◽

Goutam Rath ◽

Rayasa Murthy ◽

Umesh Gupta ◽

Palakkod Vatsala ◽

...

Keyword(s):

Drug Resistance ◽

Drug Molecules ◽

Effective Delivery

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Computational and Experimental Binding Mechanism of DNA-drug Interactions

Current Pharmaceutical Design ◽

10.2174/1381612824666181106101448 ◽

2019 ◽

Vol 24 (32) ◽

pp. 3739-3757 ◽

Cited By ~ 2

Author(s):

Chandrabose Selvaraj ◽

Sanjeev K. Singh

Keyword(s):

Small Molecules ◽

Self Assembly ◽

Genetic Material ◽

Dna Interaction ◽

Significant Feature ◽

Drug Molecules ◽

Potential Applications ◽

Novel Drug ◽

Groove Binders ◽

Molecular Docking And Dynamics

Nucleic acid is the key unit and a predominant genetic material for interpreting the fundamental basis of genetic information in an organism and now it is used for the evolution of a novel group of therapeutics. To identify the potential impact on the biological science, it receives high recognition in therapeutic applications. Due to its selective recognition of molecular targets and pathways, DNA significantly imparts tremendous specificity of action. Examining the properties of DNA holds numerous advantages in assembly, interconnects, computational elements, along with potential applications of DNA self-assembly and scaffolding include nanoelectronics, biosensors, and programmable/autonomous molecular machines. The interaction of low molecular weight, small molecules with DNA is a significant feature in pharmacology. Based on the mode of binding mechanisms, small molecules are categorized as intercalators and groove binders having a significant role in target-based drug development. The understanding mechanism of drug-DNA interaction plays an important role in the development of novel drug molecules with more effective and lesser side effects. This article attempts to outline those interactions of drug-DNA with both experimental and computational advances, including ultraviolet (UV) -visible spectroscopy, fluorescent spectroscopy, circular dichroism, nuclear magnetic resonance (NMR), molecular docking and dynamics, and quantum mechanical applications.

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Recent Review on Subclass B1 Metallo-β-lactamases Inhibitors: Sword for Antimicrobial Resistance

Current Drug Targets ◽

10.2174/1389450120666181217101812 ◽

2019 ◽

Vol 20 (7) ◽

pp. 756-762 ◽

Cited By ~ 2

Author(s):

Aditi Kaushik ◽

Manish Kaushik ◽

Viney Lather ◽

J.S. Dua

Keyword(s):

Antibiotic Resistance ◽

Multidrug Resistance ◽

Antimicrobial Resistance ◽

Global Health ◽

Human Health ◽

Microbial Pathogens ◽

Present Review ◽

Drug Molecules ◽

Global Threat ◽

Powerful Strategy

An emerging crisis of antibiotic resistance for microbial pathogens is alarming all the nations, posing a global threat to human health. The production of the metallo-β-lactamase enzyme is the most powerful strategy of bacteria to produce resistance. An efficient way to combat this global health threat is the development of broad/non-specific type of metallo-β-lactamase inhibitors, which can inhibit the different isoforms of the enzyme. Till date, there are no clinically active drugs against metallo- β-lactamase. The lack of efficient drug molecules against MBLs carrying bacteria requires continuous research efforts to overcome the problem of multidrug-resistance bacteria. The present review will discuss the clinically potent molecules against different variants of B1 metallo-β-lactamase.

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Structure and Activity of Pentacyclic Triterpenes Codrugs. A Review

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666210105110848 ◽

2021 ◽

Vol 21 ◽

Author(s):

Justyna Żwawiak ◽

Anna Pawełczyk ◽

Dorota Olender ◽

Lucjusz Zaprutko

Keyword(s):

Biological Activities ◽

Anticancer Activities ◽

Drug Molecule ◽

Pentacyclic Triterpene ◽

Formation Pathway ◽

Chemical Systems ◽

Drug Molecules ◽

Wide Range ◽

Anti Hiv ◽

Structure And Activity

: Triterpenes are a wide and important group of compounds that have several promising pharmacological properties, such as hepatoprotective, anti-inflammatory, anti-HIV, antioxidant, or anticancer activities. Such potent substances can be successfully incorporated in more complex chemical systems e.g. codrugs or pro-drugs that have better pharmacological profile. The codrug is connected with a drug formation pathway to chemically cohere at least two drug molecules to improve positive therapeutic efficiency or decrease side effects. The codrug can be cleaved in the organism to generate effective compounds previously used as substrates. This article presents an overview of codrugs that consist of pentacyclic triterpene moiety that is chosen as a basic codrug moiety due to their wide range of vital activities and another drug molecule fragment. It was found that triterpenoid codrugs are characterized by a wide range of biological activities. However, most of them have anticancer potency.

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Recent Updates on Development of Drug Molecules for Human African Trypanosomiasis

Current Topics in Medicinal Chemistry ◽

10.2174/1568026616666160413125335 ◽

2016 ◽

Vol 16 (20) ◽

pp. 2245-2265 ◽

Cited By ~ 16

Author(s):

Ajmer Singh Grewal ◽

Deepti Pandita ◽

Shashikant Bhardwaj ◽

Viney Lather

Keyword(s):

Human African Trypanosomiasis ◽

African Trypanosomiasis ◽

Drug Molecules

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