Replacing sulfa drugs with novel DHPS inhibitors
Dalia I Hammoudeh1, Ying Zhao, Stephen W White
1Department of Structural Biology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Abstract:
More research effort needs to be invested in antimicrobial drug development to address the increasing threat of multidrug-resistant organisms. The enzyme DHPS has been a validated drug target for over 70 years as the target for the highly successful sulfa drugs. The use of sulfa drugs has been compromised by the widespread presence of resistant organisms and the adverse side effects associated with their use. Despite the large amount of structural information available for DHPS, few recent publications address the possibility of using this knowledge for novel drug design. This article reviews the relevant papers and patents that report promising new small-molecule inhibitors of DHPS, and discuss these data in light of new insights into the DHPS catalytic mechanism and recently determined crystal structures of DHPS bound to potent small-molecule inhibitors. This new functional understanding confirms that DHPS deserves further consideration as an antimicrobial drug target.
More Related Videos
Related Concept Videos
Oral Hypoglycemic Agents: Sulfonylureas
Combined Effects of Drugs: Synergism
Such synergistic combinations...
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
Antihypertensive Drugs: Thiazide-Class Diuretics
Drugs for Treatment of Ulcerative Colitis in IBD
Phase II Reactions: Miscellaneous Conjugation Reactions
A key example involves the conjugation of cyanide ions, which impair cellular respiration and alter hemoglobin into non-oxygen-carrying cyanmethemoglobin. To neutralize this threat, a sulfur atom from thiosulphate is transferred to the cyanide ion, catalyzed by the enzyme rhodanese, resulting in an inactive compound called thiocyanate. The production of...


