Naturally Occurring Pyrrolizidines: Inhibition of α-Glucosidase 1 and Anti-HIV Activity of One Stereoisomer

1992 ◽  
Vol 3 (5) ◽  
pp. 273-277 ◽  
Author(s):  
D. L. Taylor ◽  
R. Nash ◽  
L. E. Fellows ◽  
M. S. Kang ◽  
A. S. Tyms
Keyword(s):  
Inhibitory Activity ◽  
Pyrrolizidine Alkaloid ◽  
Virus Growth ◽  
Processing Enzymes ◽  
Naturally Occurring ◽  
Antiviral Effects ◽  
Castanospermum Australe ◽  
Glycoprotein Processing ◽  
Anti Hiv ◽  
Hiv 1

Alexine, a naturally occurring pyrrolizidine alkaloid, isolated from Alexa leiopetala, and four stereoisomers, isolated from Castanospermum australe, were investigated for inhibitory activity against the growth of HIV-1. Only treatment with the 7,7a-diepialexine restricted virus growth (IC50 0.38 mm) although it was less active than the indolizidine alkaloid castanospermine (IC50 0.02 mm). The antiviral effects of 7,7a-diepialexine, like castanospermine, correlated with the inhibitory activity against purified pig kidney α-glucosidase 1 of the glycoprotein processing enzymes and the reduced cleavage of the precursor HIV-1 glycoprotein gp160.

Synthesis and anti-HIV Activity of New Fused Chromene Derivatives Derived from 2-Amino-4-(1-naphthyl)-5-oxo-4H,5H-pyrano[3,2- c]chromene-3-carbonitrile

2013 ◽  
Vol 68 (3) ◽  
pp. 229-238 ◽  
Author(s):  
Najim A. Al-Masoudi ◽  
Hamid H. Mohammed ◽  
Aws M. Hamdy ◽  
Omer A. Akrawi ◽  
Nadi Eleya ◽  
...  
Keyword(s):  
Spectral Data ◽  
Inhibitory Activity ◽  
Activity Screening ◽  
Anti Hiv ◽  
Hiv 1

A new series of pyrano-chromene and pyrimido pyrano-chromene derivatives were synthesized starting from 2-amino-4-(1-naphthyl)-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile (6). The structures of the synthesized compounds were elucidated by spectral data. Compounds 6-11, 13-15 and 18 have been selected for an inhibitory activity screening against HIV-1 and HIV-2 in MT-4 cells.

scholarly journals Inhibition of Human Immunodeficiency Virus Type 1 Infectivity by Secretory Leukocyte Protease Inhibitor Occurs Prior to Viral Reverse Transcription

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1141-1149 ◽  
Author(s):  
Tessie B. McNeely ◽  
Diane C. Shugars ◽  
Mary Rosendahl ◽  
Christina Tucker ◽  
Stephen P. Eisenberg ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitor ◽  
Viral Infection ◽  
Reverse Transcription ◽  
Inhibitory Activity ◽  
Virus Binding ◽  
Viral Dna ◽  
Immunodeficiency Virus ◽  
Anti Hiv ◽  
Hiv 1

Abstract Infection of monocytes with human immunodeficiency virus type 1Ba-L (HIV-1Ba-L ) is significantly inhibited by treatment with the serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI). SLPI does not appear to act on virus directly, but rather the inhibitory activity is most likely due to interaction with the host cell. The current study was initiated to investigate how SLPI interacts with monocytes to inhibit infection. SLPI was found to bind to monocytes with high affinity to a single class of receptor sites (∼7,000 receptors per monocyte, KD = 3.6 nmol/L). The putative SLPI receptor was identified as a surface protein with a molecular weight of 55 ± 5 kD. A well-characterized function of SLPI is inhibition of neutrophil elastase and cathepsin G. However, two SLPI mutants (or muteins) that contain single amino acid substitutions and exhibit greatly reduced protease inhibitory activity still bound to monocytes and retained anti–HIV-1 activity. SLPI consists of two domains, of which the C-terminal domain contains the protease inhibiting region. However, when tested independently, neither domain had potent anti–HIV-1 activity. SLPI binding neither prevented virus binding to monocytes nor attenuated the infectivity of any virus progeny that escaped inhibition by SLPI. A polymerase chain reaction (PCR)-based assay for newly generated viral DNA demonstrated that SLPI blocks at or before viral DNA synthesis. Therefore, it most likely inhibits a step of viral infection that occurs after virus binding but before reverse transcription. Taken together, the unique antiviral activity of SLPI, which may be independent of its previously characterized antiprotease activity, appears to reside in disruption of the viral infection process soon after virus binding.

scholarly journals Anti-HIV-1 activity in human primary cells and Anti-HIV-1 RT inhibitory activity of extracts from the red seaweed Acanthophora spicifera

2016 ◽  
Vol 10 (35) ◽  
pp. 621-625 ◽  
Author(s):  
Cesar Richter Nogueira Caio ◽  
Christina Nunes de Palmer Paixão Izabel ◽  
Cesar Cirne-Santos Claudio ◽  
Roberto Soares Stephens Paulo ◽  
Campos Villaça Roberto ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Red Seaweed ◽  
Primary Cells ◽  
Human Primary Cells ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Multivalent agents containing 1-substituted 2,3,4-trihydroxyphenyl moieties as novel synthetic polyphenols directed against HIV-1

2014 ◽  
Vol 12 (28) ◽  
pp. 5278-5294 ◽  
Author(s):  
Aida Flores ◽  
María José Camarasa ◽  
María Jesús Pérez-Pérez ◽  
Ana San-Félix ◽  
Jan Balzarini ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Naturally Occurring ◽  
Hydrolysable Tannins ◽  
Hiv 1

A series of synthetic polyphenols inspired by the multivalent architecture of naturally-occurring hydrolysable tannins exhibited selective inhibitory activity against HIV-1.

scholarly journals Synergistic Combinations of the CCR5 Inhibitor VCH-286 with Other Classes of HIV-1 Inhibitors

2014 ◽  
Vol 58 (12) ◽  
pp. 7565-7569 ◽  
Author(s):  
Odalis Asin-Milan ◽  
Mohamed Sylla ◽  
Mohamed El-Far ◽  
Geneviève Belanger-Jasmin ◽  
Alpha Haidara ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Single Agent ◽  
Drug Classes ◽  
Additive Interactions ◽  
Anti Hiv ◽  
Ccr5 Inhibitor ◽  
Synergistic Combinations ◽  
Hiv 1

ABSTRACTHere, we evaluated thein vitroanti-HIV-1 activity of the experimental CCR5 inhibitor VCH-286 as a single agent or in combination with various classes of HIV-1 inhibitors. Although VCH-286 used alone had highly inhibitory activity, paired combinations with different drug classes led to synergistic or additive interactions. However, combinations with other CCR5 inhibitors led to effects ranging from synergy to antagonism. We suggest that caution should be exercised when combining CCR5 inhibitorsin vivo.

scholarly journals The Potent Anti-HIV Activity of CXCL12γ Correlates with Efficient CXCR4 Binding and Internalization

2009 ◽  
Vol 84 (5) ◽  
pp. 2563-2572 ◽  
Author(s):  
Jeffrey D. Altenburg ◽  
Qingwen Jin ◽  
Bashar Alkhatib ◽  
Ghalib Alkhatib
Keyword(s):  
Antiviral Activity ◽  
Stromal Cell ◽  
Chemotactic Activity ◽  
Receptor Internalization ◽  
Potent Antiviral Activity ◽  
Naturally Occurring ◽  
Conserved Domain ◽  
Stromal Cell Derived Factor ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT We previously demonstrated that the naturally occurring splice variant stromal cell-derived factor 1γ/CXCL12γ is the most potent CXCL12 isoform in blocking X4 HIV-1, with weak chemotactic activity. A conserved BBXB domain (B for basic and X for any residue) located in the N terminus (24KHLK27) is found in all six isoforms of CXCL12. To determine whether the potent antiviral activity of CXCL12γ is due to the presence of the extra C-terminal BBXB domains, we mutated each domain individually as well as in combination. Although binding of CXCL12γ to heparan sulfate proteoglycan (HSPG) was 10-fold higher than that observed with CXCL12α, the results did not demonstrate a direct correlation between HSPG binding and the potent antiviral activity. CXCL12γ mutants lacking the conserved BBXB domain (designated γB1) showed increased binding to HSPG but reduced anti-HIV activity. In contrast, the mutants lacking the C-terminal second and/or third BBXB domain but retaining the conserved domain (designated B2, B3, and B23) showed decreased binding to HSPG but increased anti-HIV activity. The B2, B3, and B23 mutants were associated with enhanced CXCR4 binding, receptor internalization, and restored chemotaxis. Internalization of CXCR4 was more potent with CXCL12γ than with CXCL12α and was significantly reduced when the conserved BBXB domain was mutated. We concluded that the observed potent anti-HIV-1 activity of CXCL12γ is due to increased affinity for CXCR4 and to efficient receptor internalization.

scholarly journals Anti-HIV-1 protease activity of the crude extracts and isolated compounds from Auricularia polytricha

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chanin Sillapachaiyaporn ◽  
Sunita Nilkhet ◽  
Alison T. Ung ◽  
Siriporn Chuchawankul
Keyword(s):  
Natural Products ◽  
Inhibitory Activity ◽  
Edible Mushroom ◽  
2D Nmr ◽  
Antiretroviral Drugs ◽  
Significant Inhibition ◽  
Fatty Esters ◽  
Auricularia Polytricha ◽  
Anti Hiv ◽  
Hiv 1

Abstract Background Acquired immunodeficiency syndrome (AIDS) is caused by the Human immunodeficiency virus type-1 (HIV-1). HIV-1 protease (HIV-1 PR) is an essential enzyme for the HIV replication, and therefore, it is an important target for antiretroviral drugs development, particularly from natural products. Auricularia polytricha (AP) is an edible mushroom with several important therapeutic properties. These properties will be investigated as HIV-1 PR inhibitors. Methods The sequential hexane (APH), ethanol (APE) and water (APW) extracts from AP were screened for inhibitory activity against HIV-1 PR. The extract that consistently showed the strong HIV-1 PR inhibition was further investigated for its phytochemical constituents. The compounds were purified by column chromatography. The isolated compounds were structurally elucidated using 1D and 2D NMR, HRMS, FTIR, and GC/MS techniques. Each compound was screened against HIV-1 PR to determine its inhibitory activity and to provide an explanation for the activity found in the extract. Results Hexane crude extract of AP (APH) exhibited significant inhibition on HIV-1 PR activity. Four major compounds isolated from APH fraction were identified to be two triacylglycerols, linoleic acid and ergosterol. Moreover, all four compounds showed significant inhibition of HIV-1 PR activity. Conclusion The findings from this study suggest that AP is a good source of fatty esters, fatty acids and ergosterol. These natural products exhibit anti-HIV-1 properties by blocking HIV-1 PR. These important biological results warrant further development of AP as an alternative antiretroviral drug.

scholarly journals Recent Findings on the Mechanisms Involved in Tenofovir Resistance

2014 ◽  
Vol 23 (6) ◽  
pp. 217-222 ◽  
Author(s):  
Pinar Iyidogan ◽  
Karen S Anderson
Keyword(s):  
Drug Resistance ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Sequence Context ◽  
Antiviral Effects ◽  
Current Therapies ◽  
Viral Sequences ◽  
Anti Hiv ◽  
Hiv 1

Since its approval for clinical use in 2001, tenofovir (TFV) has become one of the most frequently prescribed nucleotide analogues used in combination with other antiretroviral agents against HIV-1 infection. Although reverse transcriptase inhibitors (RTIs) including TFV have been shown to be highly potent with reasonable safety profiles in the clinic, drug resistance hinders the effectiveness of current therapies and even causes treatment failure. Therefore, understanding the resistance mechanisms of RT and exploring the potential antiviral synergy between the different RTIs in combination therapies against the resistance mechanisms would greatly improve the long-term efficacy of existing and future regimens. We have studied the pyrophosphorolytic removal of TFV, a major resistance mechanism that RT utilizes, from two different viral sequences and observed interesting outcomes associated with the sequence context. Furthermore, addition of efavirenz, a non-nucleoside RTI, inhibits this removal process confirming the synergistic antiviral effects. This article highlights our recently published work on the viral sequence context contributing to the study of anti-HIV drug resistance in conjunction with the benefits of combining various RTIs that may have been neglected previously.

scholarly journals Inhibition of Human Immunodeficiency Virus Type 1 Infectivity by Secretory Leukocyte Protease Inhibitor Occurs Prior to Viral Reverse Transcription

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1141-1149 ◽  
Author(s):  
Tessie B. McNeely ◽  
Diane C. Shugars ◽  
Mary Rosendahl ◽  
Christina Tucker ◽  
Stephen P. Eisenberg ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitor ◽  
Viral Infection ◽  
Reverse Transcription ◽  
Inhibitory Activity ◽  
Virus Binding ◽  
Viral Dna ◽  
Immunodeficiency Virus ◽  
Anti Hiv ◽  
Hiv 1

Infection of monocytes with human immunodeficiency virus type 1Ba-L (HIV-1Ba-L ) is significantly inhibited by treatment with the serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI). SLPI does not appear to act on virus directly, but rather the inhibitory activity is most likely due to interaction with the host cell. The current study was initiated to investigate how SLPI interacts with monocytes to inhibit infection. SLPI was found to bind to monocytes with high affinity to a single class of receptor sites (∼7,000 receptors per monocyte, KD = 3.6 nmol/L). The putative SLPI receptor was identified as a surface protein with a molecular weight of 55 ± 5 kD. A well-characterized function of SLPI is inhibition of neutrophil elastase and cathepsin G. However, two SLPI mutants (or muteins) that contain single amino acid substitutions and exhibit greatly reduced protease inhibitory activity still bound to monocytes and retained anti–HIV-1 activity. SLPI consists of two domains, of which the C-terminal domain contains the protease inhibiting region. However, when tested independently, neither domain had potent anti–HIV-1 activity. SLPI binding neither prevented virus binding to monocytes nor attenuated the infectivity of any virus progeny that escaped inhibition by SLPI. A polymerase chain reaction (PCR)-based assay for newly generated viral DNA demonstrated that SLPI blocks at or before viral DNA synthesis. Therefore, it most likely inhibits a step of viral infection that occurs after virus binding but before reverse transcription. Taken together, the unique antiviral activity of SLPI, which may be independent of its previously characterized antiprotease activity, appears to reside in disruption of the viral infection process soon after virus binding.

scholarly journals Inhibition of gp120 Binding to the CD4 Antigen by Dyes: Mechanism of Effect and Contribution to anti-HIV Activity

1992 ◽  
Vol 3 (1) ◽  
pp. 49-53 ◽  
Author(s):  
M. R. Kozlowski ◽  
A. Watson
Keyword(s):  
Binding Isotherm ◽  
Activity Inhibition ◽  
Viral Binding ◽  
Antiviral Effects ◽  
Gp120 Binding ◽  
Novel Drugs ◽  
Binding Inhibition ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Putative Mechanism

Several compounds developed for use as dyes have shown activity against HIV-1. The present study examines one putative mechanism of this anti-HIV activity, inhibition of gp120/CD4 binding, and its contribution to the antiviral effects of three chemical classes of dyes. Although, for most dyes, the ability to inhibit gp120/CD4 binding and the reported anti-HIV activities do not correlate, a group of dyes is identified whose anti-HIV activity does appear to be related to binding inhibition. Qualitative examination of the effect of two of these dyes on the gp120/CD4 binding isotherm suggests that the inhibition is non-competitive. Dyes which act by preventing viral binding may represent prototypes for the development of novel drugs for the treatment or prevention of AIDS.

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