Combating the threat of anthrax: a quantitative structure-activity relationship approach.
Bacterial agents or products more likely to be used as biological weapons of mass destruction are Bacillus anthracis, Francisella tularensis, Yersinia pestis, and the neurotoxin of Clostridium botulinum. Anthrax is an acute infectious disease with a high mortality rate caused by Bacillus anthracis, reinforcing the need for better adjunctive therapy and prevention strategies. In this paper, we developed 7 QSAR models on penicillin-based inhibitors of the class A and B beta-lactamases from B. anthracis and inhibitors of anthrax lethal factor to understand the chemical-biological interactions. Hydrophobic and steric factors are found to be the most important determinants of the activity. Internal (cross-validation ( q (2)), quality factor ( Q), Fischer statistics ( F), and Y-randomization) and external validation tests have validated all the QSAR models.
Verma
Rajeshwar P
RP
Department of Chemistry, Pomona College, Claremont, CA 91711, USA. rverma@pomona.edu
Hansch
Corwin
C
D000881:Anthrax / Q000188:drug therapy / Q000517:prevention & control; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000737:chemistry; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000737:chemistry; D003198:Computer Simulation; D015195:Drug Design; D005663:Furans / Q000737:chemistry / Q000494:pharmacology; D008954:Models, Biological; D015394:Molecular Structure; D010406:Penicillins / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D012236:Rhodanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry
D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D005663:Furans; D010406:Penicillins; C030325:anthrax toxin; D065093:beta-Lactamase Inhibitors; D012236:Rhodanine; D001618:beta-Lactamases