171744-39-1Relevant articles and documents
The design and synthesis of redox core-alpha amino acid composites based on thiol-disulfide exchange mechanism and a comparative study of their zinc abstraction potential from [CCXX] boxes in proteins
Ranganathan, Subramania,Muraleedharan,Bharadwaj, Parimal,Chatterji, Dipankar,Karle, Isabella
, p. 2861 - 2874 (2007/10/03)
The design and synthesis of agents that can abstract zinc from their [CCXX] (C=cysteine; X=cysteine/histidine) boxes by thiol-disulfide exchange-having as control, the redox parities of the core sulfur ligands of the reagent and the enzyme, has been illustrated, and their efficiency demonstrated by monitoring the inhibition of the transcription of calf thymus DNA by E. coli RNA polymerase, which harbors two zinc atoms in their [CCXX] boxes of which one is exchangeable. Maximum inhibition possible with removal of the exchangeable zinc was seen with redox-sulfanilamide-glutamate composite. In sharp contrast, normal chelating agents (EDTA, phenanthroline) even in a thousand fold excess showed only marginal inhibition, thus supporting an exchange mechanism for the metal removal.
Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HIV-1 agents that target the viral nucleocapsid protein zinc fingers
Turpin, Jim A.,Song, Yongsheng,Inman, John K.,Huang, Mingjun,Wallqvist, Anders,Maynard, Andrew,Covell, David G.,Rice, William G.,Ettore, Appella
, p. 67 - 86 (2007/10/03)
Nucleocapsid p7 protein (NCp7) zinc finger domains of the human immunodeficiency virus type 1 (HIV-1) are being developed as antiviral targets due to their key roles in vital replication and their mutationally nonpermissive nature. On the basis of our exp
A new class of anti-HIV-1 agents targeted toward the nucleocapsid protein NCp7: The 2,2'-dithiobisbenzamides
Domagala, John M.,Bader, John P.,Gogliotti, Rocco D.,Sanchez, Joseph P.,Stier, Michael A.,Song, Yuntao,Vara Prasad,Tummino, Peter J.,Scholten, Jeffrey,Harvey, Patricia,Holler, Tod,Gracheck, Steve,Hupe, Donald,Rice, William G.,Schultz, Robert
, p. 569 - 579 (2007/10/03)
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 μM anti-HIV agents with simple chemical structures were identified as possible chemotherapeutic agents for the treatment of AIDS.
