Related Experiment Video
Updated: Jun 14, 2025

Nucleoside Triphosphates - From Synthesis to Biochemical Characterization
Published on: April 3, 2014
Enhancing the therapeutic window for Spectinamide anti-tuberculosis Agents: Synthesis, Evaluation, and activation of
Jiuyu Liu1, Pradeep B Lukka2, Victoria A Ektnitphong3
1Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, United States.
Abstract:
Spectinamides are a novel class of narrow-spectrum antitubercular agents with the potential to treat drug-resistant tuberculosis infections. Spectinamide 1810 has shown a good safety record following subcutaneous injection in mice or infusion in rats but exhibits transient acute toxicity following bolus administration in either species. To improve the therapeutic index of 1810, an injectable prodrug strategy was explored. The injectable phosphate prodrug 3408 has a superior maximum tolerated dose compared to 1810 or Gentamicin. Following intravenous administration in rodents, prodrug 3408 was quickly converted to 1810. The resulting 1810 exposure and pharmacokinetic profile after 3408 administration was identical to equivalent molar amounts of 1810 given directly by intravenous administration. 3408 and the parent 1810 exhibited similar overall efficacy in a BALB/c acute tuberculosis efficacy model. Delivery of 1810 in phosphate prodrug form, therefore, holds the potential to improve further the therapeutic index of an already promising tuberculosis antibiotic.
Related Concept Videos
Drug Metabolism: Phase II Reactions
Prodrugs
Prodrugs help overcome...
Phase II Reactions: Sulfation and Conjugation with α-Amino Acids
Drug Biotransformation: Overview
Drug Administration and Therapy Phases: Overview
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
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...

