+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

A new class of anti-HIV-1 agents targeted toward the nucleocapsid protein NCp7: the 2,2'-dithiobisbenzamides

A new class of anti-HIV-1 agents targeted toward the nucleocapsid protein NCp7: the 2,2'-dithiobisbenzamides

Bioorganic and Medicinal Chemistry 5(3): 569-579

As part of the National Cancer Institute's Drug Screening Program, a new class of antiretrovirals active against the human immunodeficiency virus HIV-1 has been identified, and the HIV-1 nucleocapsid protein NCp7 was proposed as the target of antiviral action. The 2,2'-dithiobis-[4'-(sulfamoyl)benzanilide] (3x) and the 2,2'-dithiobis(5-acetylamino)benzamide (10) represented the prototypic lead structures. A wide variety of 2,2'-dithiobisbenzamides were prepared and tested for anti-HIV-1 activity, cytotoxicity, and their ability to extrude zinc from the zinc fingers for NCp7. The structure-activity relationships demonstrated that the ability to extrude zinc from NCp7 resided in the 2,2'-dithiobisbenzamide core structure. The 3,3' and the 4,4' isomers were inactive. While many analogs based upon the core structure retained the zinc extrusion activity, the best overall anti-HIV-1 activity was only found in a narrow set of derivatives possessing carboxylic acid, carboxamide, or phenylsulfonamide functional groups. These functional groups were more important for reducing cytotoxicity than improving antiviral potency or activity vs NCp7. All of the compounds with antiviral activity also extruded zinc from NCp7. From this study several classes of low microM anti-HIV agents with simple chemical structures were identified as possible chemotherapeutic agents for the treatment of AIDS.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 045079395

Download citation: RISBibTeXText

PMID: 9113335

DOI: 10.1016/s0968-0896(96)00269-6

Related references

Conformational changes between human immunodeficiency virus type 1 nucleocapsid protein NCp7 and its precursor NCp15 as detected by anti-NCp7 monoclonal antibodies. Journal of General Virology 76: 2457-2466, 1995

Design and Synthesis of DiselenoBisBenzamides (DISeBAs) as Nucleocapsid Protein 7 (NCp7) Inhibitors with anti-HIV Activity. Journal of Medicinal Chemistry 58(24): 9601-9614, 2016

Interaction of the HIV-1 nucleocapsid protein, NCp7, with RNA. Progress in Biophysics & Molecular Biology 65(SUPPL 1): 80, 1996

Identification of a peptide binding to the HIV-1 nucleocapsid protein (NCP7). Protein and Peptide Letters 3(6): 377-383, 1996

Comparative nucleic acid chaperone properties of the nucleocapsid protein NCp7 and Tat protein of HIV-1. Virus Research 169(2): 349-360, 2013

The prion protein has RNA binding and chaperoning properties characteristic of nucleocapsid protein NCP7 of HIV-1. Journal of Biological Chemistry 276(22): 19301-9, 2001

The zinc fingers of HIV nucleocapsid protein NCp7 direct interactions with the viral regulatory protein Vpr. Journal of Biological Chemistry 272(49): 30753-9, 1998

Nucleomimetic strategy for the inhibition of HIV-1 nucleocapsid protein NCp7 activities. Bioorganic & Medicinal Chemistry Letters 9(4): 627-632, Feb 22, 1999

Evidence of interactions between the nucleocapsid protein NCp7 and the reverse transcriptase of HIV-1. Journal of Biological Chemistry 274(16): 11283-8, 1999

Au(iii) compounds as HIV nucleocapsid protein (NCp7)-nucleic acid antagonists. Chemical Communications 53(1): 91-94, 2016

Studies on the mechanism of inactivation of the HIV-1 nucleocapsid protein NCp7 with 2-mercaptobenzamide thioesters. Journal of Medicinal Chemistry 48(8): 2847-2858, 2005

In vitro characterization of peptides interfering with the HIV-1 nucleocapsid protein (NCp7) functions. Protein and Peptide Letters 4(5): 299-306, 1997

Nucleic acid sequence discrimination by the HIV-1 nucleocapsid protein NCp7: a fluorescence study. Biochemistry (American Chemical Society) 38(51): 816-25, 1999