Anthrax lethal factor inhibitors as potential countermeasure of the infection.

Abstract

Anthrax Lethal Factor (LF) is a zinc-dependent metalloprotease, one of the virulence factor of anthrax infection. Three forms of the anthrax infection have been identified: cutaneous (through skin), gastrointestinal (through alimentary tract), and pulmonary (by inhalation of spores). Anthrax toxin is composed of protective antigen (PA), lethal factor (LF), and edema factor (EF). Protective antigen mediates the entry of Lethal Factor/Edema Factor into the cytosol of host cells. Lethal factor (LF) inactivates mitogen-activated protein kinase kinase inducing cell death, and EF is an adenylyl cyclase impairing host defenses. In the past few years, extensive studies are undertaken to design inhibitors targeting LF. The current review focuses on the small molecule inhibitors targeting LF activity and its structure activity relationships (SAR).

• Authors: B V S Suneel Kumar, Siddharth Malik, Pradeep Grandhi, Raveendra Dayam, J A R P Sarma
• Journal: Current topics in medicinal chemistry (Curr Top Med Chem) Vol. 14 Issue 17 Pg. 1977-89 ( 2014) ISSN: 1873-4294 [Electronic] United Arab Emirates
• PMID: 25262802 (Publication Type: Journal Article, Review)

Chemical References

• Antigens, Bacterial
• Bacterial Toxins
• Protein Kinase Inhibitors
• anthrax toxin
• Mitogen-Activated Protein Kinase Kinases

Topics

• Animals
• Anthrax (drug therapy)
• Antigens, Bacterial (chemistry, metabolism)
• Bacillus anthracis (enzymology, growth & development)
• Bacterial Toxins (chemistry, metabolism)
• Humans
• Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors, metabolism)
• Models, Molecular
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Rats
• Structure-Activity Relationship