scholarly journals Characterization of the MYB-inhibitory potential of the Pan-HDAC inhibitor LAQ824

BBA Advances ◽  
2021 ◽  
pp. 100034
Author(s):  
Maria V. Yusenko ◽  
Karl-Heinz Klempnauer
Keyword(s):  
Hdac Inhibitor ◽  
Inhibitory Potential

scholarly journals Characterization of bacteriocin and chitinase producing bacterial isolates with broad-spectrum antimicrobial activities

2021 ◽  
Vol 3 (8) ◽  
Author(s):  
Muhammad Yasir ◽  
Basit Zeshan ◽  
Nur Hardy A. Daud ◽  
Izzah Shahid ◽  
Hafza Khalid
Keyword(s):  
Antimicrobial Activity ◽  
Inhibitory Activity ◽  
Antifungal Drugs ◽  
Proteinase K ◽  
Diffusion Method ◽  
List Type ◽  
Bacterial Isolates ◽  
E Coli ◽  
Inhibitory Potential

Abstract There is a need for more efficient and eco-friendly approaches to overcome increasing microbial infections. Bacteriocins and chitinases from Bacillus spp. can be powerful alternatives to conventional antibiotics and antifungal drugs, respectively. The purpose of this study was to assess the inhibitory potential of bacteriocins and chitinase enzymes against multiple resistant bacterial and fungal pathogens. Bacterial isolates were selected by growth on minimal salts medium and after that were morphologically and biochemically characterized. The physiochemical characterization of bacteriocins was carried out. The inhibitory potential of bacteriocins towards six pathogenic bacteria was determined by the well diffusion assay while chitinase activity towards three fungal strains was determined by the dual plate culture assay. Two bacterial strains (WW2P1 and WRE4P2), out of nine showed inhibition of K. pneumonia, P. aeruginosa, E. coli and MRSA while WW4P2 was positive against S. typhimurium and E. coli and WRE10P2 against P. aeruginosa, S. pneumoniae. Two bacterial isolates (WW3P1 and WRE10P2) were chosen for further study on the basis of their antifungal activities. Of these, WW3P1 isolate was more effective against A. fumigatus as well as A. niger. The proteinaceous nature of the bacteriocins was confirmed by treatment of the crude extract with proteinase K. It was found that the inhibitory activity of strain WW3P1 against E. coli was highest at 20 °C, and against S. pneumoniae it was at 20 °C and pH 10 after treatment with EDTA. Inhibition by strain the WRE10P2 against P. aeruginosa was highest at 20 °C and pH 14. It was found that EDTA increased the inhibitory activity of strain WW2P1 against P. aeruginosa, K. pneumoniae and E. coli by 2 ± 0.235, 3.5 ± 0.288, 2.5 ± 1.040 times, respectively, of strain WRE4P2 against P. aeruginosa and E. coli by 2.5 ± 0.763, 2.7 ± 0.5 times, respectively, and of strain WRE10P2 against S. pneumoniae by 3 ± 0.6236 times. The isolates have promising inhibitory activity, which should be further analyzed for the commercial production of antimicrobials. Article highlights The current study aimed to isolate the microbiome from wheat plant (Triticum aestivum L.), to screen for bacteriocin production and to assess its antimicrobial activity against human pathogens. Forty-one phenotypically different bacterial colonies were subjected to bacteriocin purification from which 25 colonies showed positive reactions. These 25 bacterial isolates were screened against six different human bacterial pathogens using the well diffusion method to check the antimicrobial activity. Out of nine bacterial isolates, WW3P1 and WRE10P2 were able to degrade the chitin and utilize it as their sole energy source. Strain WRE4P2 exhibited partial inactivation in its activity against MRSA after treatment with proteinase K.

scholarly journals Synergistic Activity of Combined NS5A Inhibitors

2015 ◽  
Vol 60 (3) ◽  
pp. 1573-1583 ◽  
Author(s):  
Donald R. O'Boyle ◽  
Peter T. Nower ◽  
Min Gao ◽  
Robert Fridell ◽  
Chunfu Wang ◽  
...  
Keyword(s):  
Cooperative Interaction ◽  
Synergistic Activity ◽  
Replication Complex ◽  
New Class ◽  
Infected Cells ◽  
Inhibitory Potential ◽  
Direct Acting ◽  
Emergence Of Resistance

Daclatasvir (DCV) is a first-in-class hepatitis C virus (HCV) nonstructural 5A replication complex inhibitor (NS5A RCI) that is clinically effective in interferon-free combinations with direct-acting antivirals (DAAs) targeting alternate HCV proteins. Recently, we reported NS5A RCI combinations that enhance HCV inhibitory potentialin vitro, defining a new class of HCV inhibitors termed NS5A synergists (J. Sun, D. R. O’Boyle II, R. A. Fridell, D. R. Langley, C. Wang, S. Roberts, P. Nower, B. M. Johnson F. Moulin, M. J. Nophsker, Y. Wang, M. Liu, K. Rigat, Y. Tu, P. Hewawasam, J. Kadow, N. A. Meanwell, M. Cockett, J. A. Lemm, M. Kramer, M. Belema, and M. Gao, Nature 527:245–248, 2015, doi:10.1038/nature15711). To extend the characterization of NS5A synergists, we tested new combinations of DCV and NS5A synergists against genotype (gt) 1 to 6 replicons and gt 1a, 2a, and 3a viruses. The kinetics of inhibition in HCV-infected cells treated with DCV, an NS5A synergist (NS5A-Syn), or a combination of DCV and NS5A-Syn were distinctive. Similar to activity observed clinically, DCV caused a multilog drop in HCV, followed by rebound due to the emergence of resistance. DCV–NS5A-Syn combinations were highly efficient at clearing cells of viruses, in line with the trend seen in replicon studies. The retreatment of resistant viruses that emerged using DCV monotherapy with DCV–NS5A-Syn resulted in a multilog drop and rebound in HCV similar to the initial decline and rebound observed with DCV alone on wild-type (WT) virus. A triple combination of DCV, NS5A-Syn, and a DAA targeting the NS3 or NS5B protein cleared the cells of viruses that are highly resistant to DCV. Our data support the observation that the cooperative interaction of DCV and NS5A-Syn potentiates both the genotype coverage and resistance barrier of DCV, offering an additional DAA option for combination therapy and tools for explorations of NS5A function.

scholarly journals Characterization of a dual BET / HDAC inhibitor for treatment of pancreatic ductal adenocarcinoma

2020 ◽  
Vol 147 (10) ◽  
pp. 2847-2861 ◽  
Author(s):  
Xin Zhang ◽  
Tim Zegar ◽  
Tim Weiser ◽  
Feda H. Hamdan ◽  
Benedict‐Tilman Berger ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Hdac Inhibitor ◽  
Ductal Adenocarcinoma

scholarly journals Structural Insights of Three 2,4-Disubstituted Dihydropyrimidine-5-carbonitriles as Potential Dihydrofolate Reductase Inhibitors

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3286
Author(s):  
Lamya H. Al-Wahaibi ◽  
Althaf Shaik ◽  
Mohammed A. Elmorsy ◽  
Mohammed S. M. Abdelbaky ◽  
Santiago Garcia-Granda ◽  
...  
Keyword(s):  
Water Molecule ◽  
Dihydrofolate Reductase ◽  
Crystal Packing ◽  
Docking Simulation ◽  
X Ray Diffraction ◽  
Space Groups ◽  
Reductase Inhibitors ◽  
Inhibitory Potential ◽  
Human Dihydrofolate Reductase

In this report, we describe the structural characterization of three 2,4-disubstituted-dihydropyrimidine-5-carbonitrile derivatives, namely 2-{[(4-nitrophenyl)methyl]sulfanyl}-6-oxo-4-propyl-1,6-dihydropyrimidine-5-carbonitrile 1, 4-(2-methylpropyl)-2-{[(4-nitrophenyl)methyl]sulfanyl}-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 2, and 2-[(2-ethoxyethyl)sulfanyl]-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitrile monohydrate 3. An X-ray diffraction analysis revealed that these compounds were crystallized in the centrosymmetric space groups and adopt an L-shaped conformation. One of the compounds (3) crystallized with a water molecule. A cyclic motif (R22(8)) mediated by N–H···O hydrogen bond was formed in compounds 1 and 2, whereas the corresponding motif was not favorable, due to the water molecule, in compound 3. The crystal packing of these compounds was analyzed based on energy frameworks performed at the B3LYP/6-31G(d,p) level of theory. Various inter-contacts were characterized using the Hirshfeld surface and its associated 2D-fingerprint plots. Furthermore, a molecular docking simulation was carried out to assess the inhibitory potential of the title compounds against the human dihydrofolate reductase (DHFR) enzyme.

scholarly journals Structure–function engineering of novel fish gelatin-derived multifunctional peptides using high-resolution peptidomics and bioinformatics

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Armin Mirzapour-Kouhdasht ◽  
Marzieh Moosavi-Nasab ◽  
Chul Won Lee ◽  
Hyosuk Yun ◽  
Jong-Bang Eun
Keyword(s):  
Three Dimensional ◽  
Fish Gelatin ◽  
Biological Characterization ◽  
Dpp Iv ◽  
Food Borne ◽  
Inhibitory Potential ◽  
Multifunctional Peptides ◽  
Multifunctional Properties

AbstractThe multifunctional properties of fish gelatin hydrolysates have not been completely elucidated. Here, the biological characterization of these peptides was performed to engineer multifunctional peptides. Bioactive peptides were produced from mackerel byproducts via successive enzymatic hydrolysis reactions using subtilisin A and actinidin as microbial and herbal proteases. The antibacterial activity against both gram-negative and -positive food-borne pathogens, including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae, as well as the inhibitory potential of angiotensin-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV), was accessed in vitro. The synthesized peptides demonstrated multifunctional properties, which were further confirmed by in silico protocols. The ACE and DPP-IV inhibitory (IC50) values of P1, P2, and P3 were 0.92 and 0.87, 0.51 and 0.93, 0.78 and 1.16 mg mL−1, respectively. Moreover, the binding energy was sufficient for all three peptides to inhibit both ACE and DPP-IV enzymes with excellent three-dimensional conformation (RMSD = 0.000) for all six docking mechanisms.

scholarly journals Biological and Chemical Characterizations of Allelopathic Potential of Diverse Accessions of the Cover Crop Sunn Hemp

2015 ◽  
Vol 140 (6) ◽  
pp. 532-541 ◽  
Author(s):  
Muhammad Mansoor Javaid ◽  
Manish Bhan ◽  
Jodie V. Johnson ◽  
Bala Rathinasabapathi ◽  
Carlene A. Chase
Keyword(s):  
Cover Crop ◽  
The United States ◽  
Water Soluble ◽  
Charge Ratio ◽  
Allelopathic Effect ◽  
Radicle Growth ◽  
Allelopathic Potential ◽  
Sunn Hemp ◽  
Inhibitory Potential

There has been increasing interest in recent years in sunn hemp (Crotalaria juncea), as a leguminous cover crop and green manure, for weed and pest management and improving soil health. Aqueous extracts and ground shoot tissue have previously been demonstrated to be phytotoxic. To further explore its allelopathic potential, bioassays and chemical characterization of water-soluble eluates of sunn hemp were undertaken. Lettuce (Lactuca sativa) radicle growth inhibition was conducted with aqueous eluates from thinly sliced sunn hemp leaves, stems, and seeds, and all three tissues exhibited the inhibitory potential. Fourteen accessions originating from the United States, India, Brazil, South Africa, Pakistan, and Nigeria had water-soluble allelochemicals in leaves, suggesting that allelopathic potential is widely distributed in this species. The highest level of inhibitory potential was found in accession IN-86. Further characterization of IN-86 leaf eluates indicated that the inhibitory compound(s) was/were not soluble in chloroform, but was/were stable when boiled for 15 minutes and resistant to 1 n HCl. Binding and elution from AG-1(OH−) ion-exchange resin also were observed. An analysis of leaf eluates of IN-86 using high-performance liquid chromatography (HPLC) followed by mass spectrometry (MS) showed the presence of a compound with a mass-to-charge ratio of 148, consistent with the spectrum for hydroxynorleucine, a phytotoxic nonprotein amino acid previously reported in seeds of C. juncea. However, its low concentration (<1 μg·mL−1) suggested that other components of the eluate were responsible for the observed allelopathic effect. The results indicate the feasibility for development of weed control strategies using allelochemicals derived from sunn hemp biomass of select genotypes IN-86, NG-71, and BR-20 from India, Nigeria, and Brazil, respectively.

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