Mechanistic differences between in vitro assays for hydrazone-based small molecule inhibitors of anthrax lethal factor.
A systematically generated series of hydrazones were analyzed as potential inhibitors of anthrax lethal factor. The hydrazones were screened using one UV-based and two fluorescence-based in vitro assays. The study identified several inhibitors with IC50 values in the micromolar range, and importantly, significant differences in the types of inhibition were observed with the different assays.
Hanna
M Leslie
ML
Chemistry and Materials Science Directorate, Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA 94551, USA.
Tarasow
Theodore M
TM
Perkins
Julie
J
D000447:Aldehydes / Q000737:chemistry; D000942:Antigens, Bacterial / Q000737:chemistry*; D001408:Bacillus anthracis / Q000737:chemistry / Q000201:enzymology; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006834:Hydrazines / Q000737:chemistry; D006835:Hydrazones / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000447:Aldehydes; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; D006834:Hydrazines; D006835:Hydrazones; C030325:anthrax toxin; D020929:Mitogen-Activated Protein Kinase Kinases