2003
DOI: 10.1002/jat.903
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Therapy and prophylaxis of inhaled biological toxins

Abstract: This review highlights the current lack of therapeutic and prophylactic treatments for use against inhaled biological toxins, especially those considered as potential biological warfare (BW) or terrorist threats. Although vaccine development remains a priority, the use of rapidly deployable adjunctive therapeutic or prophylactic drugs could be life-saving in severe cases of intoxication or where vaccination has not been possible or immunity not established. The current lack of such drugs is due to many factors… Show more

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Cited by 53 publications
(49 citation statements)
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References 264 publications
(187 reference statements)
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“…It is important to note that the eight-component pharmacophore model presented in Figure 1A is a logical extension of the six-component model shown in our original work 31 and is part of an ongoing refinement of our pharmacophore for BoNT/A LC inhibition 32,33 (which is occurring as more data become available). In this study, we wanted to identify compounds containing as many pharmacophore features as possible, but with the following specific components: (1) the ACQ substructure (which incorporates pharmacophore components A, a heteroatom associated with A, and C ( Figure 1A)), (2) an ionizable amine located 6.5-9.5 Å from the centroid of the ACQ (pharmacophore component E ( Figure 1A)), and (3) at least one of the new components from our expanded pharmacophore, either F 33 (a positive ionizable moiety located 11.7-16.7 Å from the quinoline centroid) or G 33 (a hydrophobic moiety located 8.5-12.5 Å from the quinoline centroid) ( Figure 1A). Subsequently, a congeneric series of 4-amino-7-chloroquinoline-cholate-acetates, 1-3, and a tri-ACQ derivative, 4, were identified (see Scheme 1 for two-dimensional (2-D) structures of 1-3 and Figure 2 for the 2-D structure of 4).…”
Section: Resultsmentioning
confidence: 99%
See 2 more Smart Citations
“…It is important to note that the eight-component pharmacophore model presented in Figure 1A is a logical extension of the six-component model shown in our original work 31 and is part of an ongoing refinement of our pharmacophore for BoNT/A LC inhibition 32,33 (which is occurring as more data become available). In this study, we wanted to identify compounds containing as many pharmacophore features as possible, but with the following specific components: (1) the ACQ substructure (which incorporates pharmacophore components A, a heteroatom associated with A, and C ( Figure 1A)), (2) an ionizable amine located 6.5-9.5 Å from the centroid of the ACQ (pharmacophore component E ( Figure 1A)), and (3) at least one of the new components from our expanded pharmacophore, either F 33 (a positive ionizable moiety located 11.7-16.7 Å from the quinoline centroid) or G 33 (a hydrophobic moiety located 8.5-12.5 Å from the quinoline centroid) ( Figure 1A). Subsequently, a congeneric series of 4-amino-7-chloroquinoline-cholate-acetates, 1-3, and a tri-ACQ derivative, 4, were identified (see Scheme 1 for two-dimensional (2-D) structures of 1-3 and Figure 2 for the 2-D structure of 4).…”
Section: Resultsmentioning
confidence: 99%
“…1,2 As a result, these enzymes, which are responsible for the paralysis associated with botulism, are listed as category A (highest priority) biothreat agents by the Centers for Disease Control and Prevention (CDC). BoNTs are easily produced and may be delivered via food "spiking" and/or aerosol route.…”
Section: Introductionmentioning
confidence: 99%
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“…It is well known that metabolic substances or microbial spores themselves may cause allergic symptoms. Furthermore, under certain conditions some biological agents may produce chemical substances which can cause pathogenic effects in the host by poisoning (exotoxins, endotoxins and mycotoxins) [8]. These substances of biological origin are not biological agents according to the definition given in Directive 2000/54/EC [1].…”
Section: General Aspects Of Biological Agents and Their Investgationmentioning
confidence: 99%
“…For this reason, it is considered a potential biological weapon [10] [11]. Clinical signs of intoxication are to some extent dependent on the route of exposure with onset starting 1 to 6 hours after exposure [12]. Signs of inhalational intoxication include fever, respiratory problems, gastrointestinal (GI) symptoms, toxic or septic shock and death [13].…”
Section: Introductionmentioning
confidence: 99%