4638-50-0Relevant academic research and scientific papers
Application of niclosamide and analogs as small molecule inhibitors of Zika virus and SARS-CoV-2 infection
Shamim, Khalida,Xu, Miao,Hu, Xin,Lee, Emily M,Lu, Xiao,Huang, Ruili,Shah, Pranav,Xu, Xin,Chen, Catherine Z.,Shen, Min,Guo, Hui,Chen, Lu,Itkin, Zina,Eastman, Richard T.,Shinn, Paul,Klumpp-Thomas, Carleen,Michael, Sam,Simeonov, Anton,Lo, Donald C.,Ming, Guo-li,Song, Hongjun,Tang, Hengli,Zheng, Wei,Huang, Wenwei
supporting information, (2021/03/30)
Zika virus has emerged as a potential threat to human health globally. A previous drug repurposing screen identified the approved anthelminthic drug niclosamide as a small molecule inhibitor of Zika virus infection. However, as antihelminthic drugs are generally designed to have low absorption when dosed orally, the very limited bioavailability of niclosamide will likely hinder its potential direct repurposing as an antiviral medication. Here, we conducted SAR studies focusing on the anilide and salicylic acid regions of niclosamide to improve physicochemical properties such as microsomal metabolic stability, permeability and solubility. We found that the 5-bromo substitution in the salicylic acid region retains potency while providing better drug-like properties. Other modifications in the anilide region with 2′-OMe and 2′-H substitutions were also advantageous. We found that the 4′-NO2 substituent can be replaced with a 4′-CN or 4′-CF3 substituents. Together, these modifications provide a basis for optimizing the structure of niclosamide to improve systemic exposure for application of niclosamide analogs as drug lead candidates for treating Zika and other viral infections. Indeed, key analogs were also able to rescue cells from the cytopathic effect of SARS-CoV-2 infection, indicating relevance for therapeutic strategies targeting the COVID-19 pandemic.
New derivatives of salicylamides: Preparation and antimicrobial activity against various bacterial species
Pauk, Karel,Zadrazilova, Iveta,Imramovsky, Ales,Vinsova, Jarmila,Pokorna, Michaela,Masarikova, Martina,Cizek, Alois,Jampilek, Josef
, p. 6574 - 6581 (2013/10/22)
Three series of salicylanilides, esters of N-phenylsalicylamides and 2-hydroxy-N-[1-(2-hydroxyphenylamino)-1-oxoalkan-2-yl]benzamides, in total thirty target compounds were synthesized and characterized. The compounds were evaluated against seven bacterial and three mycobacterial strains. The antimicrobial activities of some compounds were comparable or higher than the standards ampicillin, ciprofloxacin or isoniazid. Derivatives 3f demonstrated high biological activity against Staphylococcus aureus (≤0.03 μmol/L), Mycobacterium marinum (≤0.40 μmol/L) and Mycobacterium kansasii (1.58 μmol/L), 3g shows activity against Clostridium perfringens (≤0.03 μmol/L) and Bacillus cereus (0.09 μmol/L), 3h against Pasteurella multocida (≤0.03 μmol/L) and M. kansasii (≤0.43 μmol/L), 3i against methicillin-resistant S. aureus and B. cereus (≤0.03 μmol/L). The structure-activity relationships are discussed for all the compounds.
