7765-79-9Relevant academic research and scientific papers
Development of ebsulfur analogues as potent antibacterials against methicillin-resistant Staphylococcus aureus
Ngo, Huy X.,Shrestha, Sanjib K.,Green, Keith D.,Garneau-Tsodikova, Sylvie
supporting information, p. S1 - S53 (2016/12/07)
Antibiotic resistance is a worldwide problem that needs to be addressed. Staphylococcus aureus is one of the dangerous “ESKAPE” pathogens that rapidly evolve and evade many current FDA-approved antibiotics. Thus, there is an urgent need for new anti-MRSA compounds. Ebselen (also known as 2-phenyl-1,2-benzisoselenazol-3(2H)-one) has shown promising activity in clinical trials for cerebral ischemia, bipolar disorder, and noise-induced hearing loss. Recently, there has been a renewed interest in exploring the antibacterial properties of ebselen. In this study, we synthesized an ebselen-inspired library of 33 compounds where the selenium atom has been replaced by sulfur (ebsulfur derivatives) and evaluated them against a panel of drug-sensitive and drug-resistant S. aureus and non-S. aureus strains. Within our library, we identified three outstanding analogues with potent activity against all S. aureus strains tested (MIC values mostly ?2?μg/mL), and numerous additional ones with overall very good to good antibacterial activity (1–7.8?μg/mL). We also characterized the time-kill analysis, anti-biofilm ability, hemolytic activity, mammalian cytotoxicity, membrane-disruption ability, and reactive oxygen species (ROS) production of some of these analogues.
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.
