scholarly journals Comparative activity of amantadine and ribavirin against influenza virus in vitro: possible clinical relevance.

1983 ◽  
Vol 23 (3) ◽  
pp. 503-505 ◽  
Author(s):  
M J Browne ◽  
M Y Moss ◽  
M R Boyd
Keyword(s):  
Influenza Virus ◽  
Clinical Relevance ◽  
Comparative Activity

Synthesis and Antimicrobial Activity of Adamantyl Substituted Pyridoxine Derivatives

2019 ◽  
Vol 16 (12) ◽  
pp. 1360-1369 ◽  
Author(s):  
Rail Khaziev ◽  
Nikita Shtyrlin ◽  
Roman Pavelyev ◽  
Raushan Nigmatullin ◽  
Raylya Gabbasova ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Lipid Membranes ◽  
Specific Activity ◽  
Tuberculosis H37rv ◽  
Microbial Pathogens ◽  
Adamantane Derivatives ◽  
Carbon Cage ◽  
H37rv Strain ◽  
Derivatives Of

Background: Adamantane derivatives possess multiple pharmacological activities such as antiviral, anticancer, antimycobacterial, antidiabetic, antiparkinsonian and others. The interest of medicinal chemists in adamantane compounds is due to their unique spatial structure, high lipophilicity, and carbon cage rigidity. As a result, these molecules can easily penetrate biological lipid membranes and often have unique target-specific activity profile. Another pharmacophore studied in this work is pyridoxine (vitamin B6). Pyridoxine plays highly important roles in living cells as a key cofactor of many enzymes. On the other hand, its molecular scaffold is a valuable structural platform which has led to the development of several launched drugs (Pyritinol, Pirisudanol, Cycletanine, Mangafodipir) and a wide number of preclinical and clinical drug candidates. Objective: The objective of this study is a synthesis of pyridoxine-adamantane and pyridoxinecyclooctane dipharmacophore molecules. The underlying idea was to assess the antibacterial and antiviral potential of such dipharmacophores, based on multiple examples of promising antiinfective agents which have in their structures adamantane and pyridoxine moieties. Another specific reason was to explore the ability of pyridoxine pharmacophore to suppress the potential of microbial pathogens to develop resistance to drug molecules. Methods: In this study, a series of pyridoxine-adamantane and pyridoxine-cyclooctane dipharmacophore molecules were synthesized based on reactions of three different cycloalkyl amines with the corresponding electrophilic derivatives of pyridoxine aldehydes, chlorides and acetates. All synthesized compounds have been tested for their in vitro activity against M. tuberculosis H37Rv strain and H3N2 (A/Aichi/2/68) influenza virus. Results: Series of pyridoxine-adamantane and pyridoxine-cyclooctane dipharmacophore molecules were synthesized based on reactions of three different cycloalkylamines with the corresponding electrophilic derivatives of pyridoxine aldehydes, chlorides and acetates. Reaction of cycloalkylamines with pyridoxine derivatives, in which meta-hydroxyl and ortho-hydroxymethyl groups are protected by acetyl groups, represents a useful alternative to reductive amination of aldehydes and nucleophilic substitution of alkyl halides. According to a tentative mechanism, it proceeds via paraand ortho-pyridinone methides which readily react with nucleophiles. None of the synthesized dipharmacophore compounds showed activity against M. tuberculosis H37Rv strain. At the same time, three compounds demonstrated some antiviral activity against H3N2 (A/Aichi/2/68) influenza virus (EC50 52-88 µg/mL) that was comparable to the activity of Amantadine, though lower than the activity of Rimantadine. The results of this work can be useful in the design of physiologically active derivatives of pyridoxine and adamantane. Conclusion: The results of this work can be useful in the design of physiologically active derivatives of pyridoxine and adamantane.

scholarly journals Homozygous MTAP deletion in primary human glioblastoma is not associated with elevation of methylthioadenosine

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yasaman Barekatain ◽  
Jeffrey J. Ackroyd ◽  
Victoria C. Yan ◽  
Sunada Khadka ◽  
Lin Wang ◽  
...  
Keyword(s):  
Clinical Relevance ◽  
Homozygous Deletion ◽  
In Vitro Models ◽  
Arginine Methyltransferase ◽  
Human Glioblastoma ◽  
Primary Glioblastoma ◽  
Methylthioadenosine Phosphorylase ◽  
Metabolomic Profiling

AbstractHomozygous deletion of methylthioadenosine phosphorylase (MTAP) in cancers such as glioblastoma represents a potentially targetable vulnerability. Homozygous MTAP-deleted cell lines in culture show elevation of MTAP’s substrate metabolite, methylthioadenosine (MTA). High levels of MTA inhibit protein arginine methyltransferase 5 (PRMT5), which sensitizes MTAP-deleted cells to PRMT5 and methionine adenosyltransferase 2A (MAT2A) inhibition. While this concept has been extensively corroborated in vitro, the clinical relevance relies on exhibiting significant MTA accumulation in human glioblastoma. In this work, using comprehensive metabolomic profiling, we show that MTA secreted by MTAP-deleted cells in vitro results in high levels of extracellular MTA. We further demonstrate that homozygous MTAP-deleted primary glioblastoma tumors do not significantly accumulate MTA in vivo due to metabolism of MTA by MTAP-expressing stroma. These findings highlight metabolic discrepancies between in vitro models and primary human tumors that must be considered when developing strategies for precision therapies targeting glioblastoma with homozygous MTAP deletion.

scholarly journals Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus haemagglutinin

2014 ◽  
Vol 95 (5) ◽  
pp. 1033-1042 ◽  
Author(s):  
Blanca García-Barreno ◽  
Teresa Delgado ◽  
Sonia Benito ◽  
Inmaculada Casas ◽  
Francisco Pozo ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Influenza A ◽  
Point Mutations ◽  
Antigenic Site ◽  
Single Amino Acid ◽  
Antigenic Structure ◽  
Human Antibody ◽  
2009 H1n1

Murine hybridomas producing neutralizing mAbs specific to the pandemic influenza virus A/California/07/2009 haemagglutinin (HA) were isolated. These antibodies recognized at least two different but overlapping new epitopes that were conserved in the HA of most Spanish pandemic isolates. However, one of these isolates (A/Extremadura/RR6530/2010) lacked reactivity with the mAbs and carried two unique mutations in the HA head (S88Y and K136N) that were required simultaneously to eliminate reactivity with the murine antibodies. This unusual requirement directly illustrates the phenomenon of enhanced antigenic change proposed previously for the accumulation of simultaneous amino acid substitutions at antigenic sites of the influenza A virus HA during virus evolution (Shih et al., Proc Natl Acad Sci USA, 104 , 6283–6288, 2007). The changes found in the A/Extremadura/RR6530/2010 HA were not found in escape mutants selected in vitro with one of the mAbs, which contained instead nearby single amino acid changes in the HA head. Thus, either single or double point mutations may similarly alter epitopes of the new antigenic site identified in this work in the 2009 H1N1 pandemic virus HA. Moreover, this site is relevant for the human antibody response, as shown by competition of mAbs and human post-infection sera for virus binding. The results are discussed in the context of the HA antigenic structure and challenges posed for identification of sequence changes with possible antigenic impact during virus surveillance.

Comparative activity of anticestode drugs—praziquantel, niclosamide and Compound 77–6, against Hymenolepis nana

1983 ◽  
Vol 57 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Suman Gupta ◽  
J. C. Katiyar
Keyword(s):  
Drug Concentration ◽  
Hymenolepis Nana ◽  
Comparative Activity

AbstractThe activity, in terms of speed of action, of three anticestode drugs against Hymenolepis nana, both in vivo and in vitro, was investigated. Praziquantel was most effective in vivo, but had little action on adult worms and cysticercoids in vitro. Niclosamide, the least effective in vivo, was highly toxic in vitro. Compound 77–6 killed adult worms and cysticercoids in vitro in 10 min and 15 min respectively at 1000 μg/ml of drug concentration, but its in viro effect was intermediate between that of praziquantel and niclosamide.

scholarly journals Comparison of Proximal Contacts of Class II Resin Composite Restorations In Vitro

2006 ◽  
Vol 31 (6) ◽  
pp. 688-693 ◽  
Author(s):  
B. A. C. Loomans ◽  
N. J. M. Opdam ◽  
F. J. M. Roeters ◽  
E. M. Bronkhorst ◽  
R. C. W. Burgersdijk
Keyword(s):  
Clinical Relevance ◽  
Resin Composite ◽  
Class Ii ◽  
Composite Restorations ◽  
Composite Restoration

Clinical Relevance When placing a Class II resin composite restoration, the use of sectional matrix systems and separation rings to obtain tight proximal contacts is recommended.

Comparison of Temperature Changes in the Pulp Chamber Induced by Various Light Curing Units, In Vitro

10.2341/05-26 ◽  
2006 ◽  
Vol 31 (2) ◽  
pp. 261-265 ◽  
Author(s):  
A. R. Yazici ◽  
A. Müftü ◽  
G. Kugel ◽  
R. D. Perry
Keyword(s):  
Clinical Relevance ◽  
Critical Factor ◽  
Pulp Chamber ◽  
Temperature Changes ◽  
Thermal Transfer ◽  
Light Curing

Clinical Relevance The thickness of the residual dentin is a critical factor in the reducing thermal transfer to pulp, and this transfer varies with the curing unit used.

scholarly journals Influenza virus hemagglutinin-specific cytotoxic T cell response induced by polypeptide produced in Escherichia coli.

1985 ◽  
Vol 162 (2) ◽  
pp. 663-674 ◽  
Author(s):  
A Yamada ◽  
M R Ziese ◽  
J F Young ◽  
Y K Yamada ◽  
F A Ennis
Keyword(s):  
Influenza Virus ◽  
Recombinant Dna ◽  
Cytotoxic T Lymphocyte ◽  
Nonstructural Protein ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Protein Immunization ◽  
Recombinant Dna Techniques

We have tested the abilities of various polypeptides of A/PR/8/34 (H1N1) virus, constructed by recombinant DNA techniques, to induce influenza virus-specific secondary cytotoxic T lymphocyte (CTL) responses. A hybrid protein (c13 protein), consisting of the first 81 amino acids of viral nonstructural protein (NS1) and the HA2 subunit of viral hemagglutinin (HA), induced H-2-restricted, influenza virus subtype-specific secondary CTL in vitro, although other peptides did not. Using a recombinant virus, the viral determinant responsible for recognition was mapped to the HA2 portion of c13 protein. Immunization of mice with c13 protein induced the generation of memory CTL in vivo. The CTL precursor frequencies of A/PR/8/34 virus- and c13 protein-immune mice were estimated as one in 8,047 and 50,312, respectively. These results indicate that c13 protein primed recipient mice, even though the level of precursor frequency was below that observed in virus-immune mice.

Effect of Influenza Virus Proteins Modulate Hemostasis in vitro and in vivo

2003 ◽  
Vol 30 (6) ◽  
pp. 596-602
Author(s):  
I. N. Zhilinskaya ◽  
L. A. Lyapina ◽  
O. I. Kiselev ◽  
I. P. Ashmarin
Keyword(s):  
Influenza Virus ◽  
Virus Proteins
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