scholarly journals Bioavailability of the amino acid-attached prodrug as a new anti-HIV agent in rats

2007 ◽  
Vol 8 (3) ◽  
pp. 263
Author(s):  
Kyung-Ae Chae ◽  
Hee-Jung Cho ◽  
Ji-Min Sung ◽  
Hee Lee ◽  
Dong-Cheol Seo ◽  
...  
Keyword(s):  
Amino Acid ◽  
Anti Hiv

scholarly journals Sensitivity of human immunodeficiency virus to bicyclam derivatives is influenced by the three-dimensional structure of gp120.

1997 ◽  
Vol 41 (12) ◽  
pp. 2616-2620 ◽  
Author(s):  
K De Vreese ◽  
I Van Nerum ◽  
K Vermeire ◽  
J Anné ◽  
E De Clercq
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
Single Amino Acid ◽  
Resistance Pattern ◽  
V3 Loop ◽  
Resistant Virus ◽  
Wild Type ◽  
Immunodeficiency Virus ◽  
Resistant Strains ◽  
Anti Hiv

The bicyclams are a new class of anti-human immunodeficiency virus (anti-HIV) compounds targeted at viral entry. From marker rescue experiments, it appears that the envelope gp120 glycoprotein plays an important role in the anti-HIV activity of the bicyclams. Bicyclam-resistant strains contain a number of amino acid changes scattered over the V2 to V5 region of gp120. Experiments aimed at estimating the relative importance of particular amino acid changes with regard to the overall resistance pattern are described. The sequences of some partially bicyclam-resistant virus strains, obtained during the resistance development process, were analyzed, and the corresponding 50% effective concentrations were determined. Selected mutations observed in bicyclam-resistant strains were introduced in the wild-type background by site-directed mutagenesis. In addition, some amino acids were back-mutated to their wild-type counterparts in an otherwise JM3100-resistant strain. The sensitivities of these mutant viruses to bicyclams were determined. Construction of chimeric viruses, carrying the V3 loop of JM3100-resistant virus in a wild-type HIV type 1 HXB2 background, enabled us to investigate the importance of the mutations in the V3 loop of JM3100-resistant virus. From the results described in the report, it can be concluded that single amino acid substitutions do not influence the observed resistance to JM3100. Also, the mutations in the V3 loop are not sufficient to engender even a partially resistant phenotype. We postulate that the overall conformation of gp120 determines the degree of sensitivity or resistance of HIV strains to bicyclams.

Anti-HIV activity of a series of cosalane amino acid conjugates

2000 ◽  
Vol 10 (22) ◽  
pp. 2505-2508 ◽  
Author(s):  
Kalpathy C Santhosh ◽  
Erik De Clercq ◽  
Christophe Pannecouque ◽  
Myriam Witvrouw ◽  
Tracy L Loftus ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Conjugates ◽  
Anti Hiv

TSAO-T Analogues Bearing Amino Acids at Position N-3 of Thymine: Synthesis and Anti-Human Immunodeficiency Virus Activity

2000 ◽  
Vol 11 (1) ◽  
pp. 61-69 ◽  
Author(s):  
C Chamorro ◽  
E De Clercq ◽  
J Balzarini ◽  
M-J Camarasa ◽  
A San-Félix
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Inhibitory Effect ◽  
Acid Moiety ◽  
Hiv Replication ◽  
Virus Activity ◽  
Immunodeficiency Virus ◽  
Amino Acid Moiety ◽  
Anti Hiv ◽  
Hiv 1

Novel analogues of the anti-HIV-1 lead compound [1-[2‘,5’-bis- O-( tert-butyldimethylsilyl)-β-D-ribofuranosyl]thymine]-3‘-spiro-5’-(4“-amino-1”,2“-oxathiole-2‘,2’-dioxide) (TSAO-T) bearing different amino acids at position N-3 of thymine were prepared and evaluated as inhibitors of HIV replication. The synthesis of the target compounds was accomplished by coupling of the appropriate TSAO intermediate with a conveniently protected (L) amino acid in the presence of BOP and triethylamine, followed by depro-tection of the amino acid moiety. Several TSAO derivatives, bearing at N-3 position of the thymine base an L-amino acid retaining the free carboxylic acid, acquired activity against HIV-2, in addition to their inhibitory effect on HIV-1.

Amino acid derivatives, part 3: New peptide and glycopeptide derivatives conjugated naphthalene. Synthesis, antitumor, anti-HIV, and BVDV evaluation

2005 ◽  
Vol 16 (7) ◽  
pp. 576-586 ◽  
Author(s):  
Najim A. Al-Masoudi ◽  
Iman A. Al-Masoudi ◽  
Ibrahim A. I. Ali ◽  
Bahjat Saeed ◽  
Palo La Colla
Keyword(s):  
Amino Acid ◽  
Amino Acid Derivatives ◽  
Anti Hiv

New Aryl-1,3-thiazole-4-carbohydrazides, Their 1,3,4-Oxadiazole-2- thione, 1,2,4-Triazole, Isatin-3-ylidene and Carboxamide Derivatives. Synthesis and Anti-HIV Activity

2012 ◽  
Vol 67 (7) ◽  
pp. 747-758 ◽  
Author(s):  
Mehwash Zia ◽  
Tashfeen Akhtar ◽  
Shahid Hameed ◽  
Najim A. Al-Masoudi
Keyword(s):  
Amino Acid ◽  
Methyl Esters ◽  
Acid Methyl ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Amino Acid Methyl Esters

A series of isatin-3-ylidene (6a-i) and arylthiazolyl-1,3,4-oxadiazole-2-thione derivatives 7a-i derived from arylthiazolyl carbohydrazide analogs 4a-i were synthesized. Analogously, coupling of 4f with various amino acid methyl esters in the presence of HOBt/DCC reagents afforded the carboxamide derivatives 9a-d. The newly synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. All compounds are inactive, except compounds 9b and 9c which showed inhibition of HIV-1 with EC50 = 2:34 μg mL-1, and 1.12 μg mL-1 with therapeutic indexes (SI) of 9 and <1, respectively.

Phosphoramidate conjugates of 3′-azido-3′-deoxythymidine glycerolipid derivatives and amino acid esters: synthesis and anti-HIV activity

2021 ◽  
Author(s):  
Elizaveta S. Darnotuk ◽  
Andrei E. Siniavin ◽  
Nikolay V. Shulga ◽  
Eduard V. Karamov ◽  
Natal’ya S. Shastina
Keyword(s):  
Amino Acid ◽  
Amino Acid Esters ◽  
Anti Hiv ◽  
Acid Esters

scholarly journals Novel Nucleoside Phosphoramidates as Inhibitors of HIV: Studies on the Stereochemical Requirements of the Phosphoramidate Amino Acid

1996 ◽  
Vol 7 (4) ◽  
pp. 184-188 ◽  
Author(s):  
C. McGuigan ◽  
A. Salgado ◽  
C. Yarnold ◽  
T.Y. Harries ◽  
E. De Clercq ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Antiviral Activity ◽  
Antiviral Effect ◽  
Amino Acid Derivatives ◽  
Free Nucleotides ◽  
Nucleoside Phosphoramidates ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Marked Dependence

Novel phosphoramidate derivatives of the anti-HIV nucleoside analogue d4T were designed to act as labile membrane-soluble prodrugs of the bio-active free nucleotide d4TMP. We herein reveal the very marked dependence of the antiviral activity of these phosphoramidates upon the stereochemistry of the amino acid attached to the phosphate centre; with a strong preference for the L-stereochemistry. These phosphate triesters were shown to liberate amino acid derivatives of the nucleotide intracellularly. These novel analogues, typified by alaninyl d4T monophosphate, may act as intracellular sources of the free nucleotides. The alaninyl d4T adducts themselves exert an antiviral effect when administered extracellularly, but again with clear distinctions between the L- and D-series. This evidence indicates that extracellularly administered blocked triesters derived from L-amino acids can generate d4TMP intracellularly, by a new pathway which is highly dependent on the amino acid stereochemistry.

Intestinal absorption and biodistribution of cosalane and its amino acid conjugates: novel anti-HIV agents

2002 ◽  
Vol 231 (2) ◽  
pp. 197-211 ◽  
Author(s):  
K.R Kuchimanchi ◽  
M.D Gandhi ◽  
R.R Sheta ◽  
T.P Johnston ◽  
K.C Santhosh ◽  
...  
Keyword(s):  
Amino Acid ◽  
Intestinal Absorption ◽  
Amino Acid Conjugates ◽  
Anti Hiv Agents ◽  
Anti Hiv

Anti-HIV-1 peptides derived from partial amino acid sequences of CC-Chemokine RANTES

2002 ◽  
Vol 10 (12) ◽  
pp. 4113-4117 ◽  
Author(s):  
Yasuhiro Nishiyama ◽  
Tsutomu Murakami ◽  
Suguru Shikama ◽  
Keisuke Kurita ◽  
Naoki Yamamoto
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequences ◽  
Cc Chemokine ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Insights into the Mechanism of Inhibition of CXCR4: Identification of Piperidinylethanamine Analogs as Anti-HIV-1 Inhibitors

2015 ◽  
Vol 59 (4) ◽  
pp. 1895-1904 ◽  
Author(s):  
Debananda Das ◽  
Kenji Maeda ◽  
Yasuhiro Hayashi ◽  
Navnath Gavande ◽  
Darshan V. Desai ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Amino Acid ◽  
Envelope Glycoprotein ◽  
Site Directed Mutagenesis ◽  
Shape Similarity ◽  
Amino Acid Substitutions ◽  
Hydrogen Bond Interactions ◽  
Computational Search ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACTThe cellular entry of HIV-1 into CD4+T cells requires ordered interactions of HIV-1 envelope glycoprotein with C-X-C chemokine receptor type 4 (CXCR4) receptors. However, such interactions, which should be critical for rational structure-based discovery of new CXCR4 inhibitors, remain poorly understood. Here we first determined the effects of amino acid substitutions in CXCR4 on HIV-1NL4-3glycoprotein-elicited fusion events using site-directed mutagenesis-based fusion assays and identified 11 potentially key amino acid substitutions, including D97A and E288A, which caused >30% reductions in fusion. We subsequently carried out a computational search of a screening library containing ∼604,000 compounds, in order to identify potential CXCR4 inhibitors. The computational search used the shape of IT1t, a known CXCR4 inhibitor, as a reference and employed various algorithms, including shape similarity, isomer generation, and docking against a CXCR4 crystal structure. Sixteen small molecules were identified for biological assays based on their high shape similarity to IT1t, and their putative binding modes formed hydrogen bond interactions with the amino acids identified above. Three compounds with piperidinylethanamine cores showed activity and were resynthesized. One molecule, designated CX6, was shown to significantly inhibit fusion elicited by X4 HIV-1NL4-3glycoprotein (50% inhibitory concentration [IC50], 1.9 μM), to inhibit Ca2+flux elicited by stromal cell-derived factor 1α (SDF-1α) (IC50, 92 nM), and to exert anti-HIV-1 activity (IC50, 1.5 μM). Structural modeling demonstrated that CX6 bound to CXCR4 through hydrogen bond interactions with Asp97 and Glu288. Our study suggests that targeting CXCR4 residues important for fusion elicited by HIV-1 envelope glycoprotein should be a useful and feasible approach to identifying novel CXCR4 inhibitors, and it provides important insights into the mechanism by which small-molecule CXCR4 inhibitors exert their anti-HIV-1 activities.

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