Thiazolide Prodrug Esters and Derived Peptides: Synthesis and Activity

IF 3.8 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

ACS Bio & Med Chem Au Pub Date : 2023-04-11 DOI:10.1021/acsbiomedchemau.2c00083

Andrew V. Stachulski*, Jean-Francois Rossignol, Sophie Pate, Joshua Taujanskas, Jonathan A. Iggo, Rudi Aerts, Etienne Pascal, Sara Piacentini, Simone La Frazia, M. Gabriella Santoro, Lieven van Vooren, Liesje Sintubin, Mark Cooper, Karl Swift and Paul M. O’Neill,

引用次数: 0

Abstract

Amino acid ester prodrugs of the thiazolides, introduced to improve the pharmacokinetic parameters of the parent drugs, proved to be stable as their salts but were unstable at pH > 5. Although some of the instability was due to simple hydrolysis, we have found that the main end products of the degradation were peptides formed by rearrangement. These peptides were stable solids: they maintained significant antiviral activity, and in general, they showed improved pharmacokinetics (better solubility and reduced clearance) compared to the parent thiazolides. We describe the preparation and evaluation of these peptides.

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噻唑类前药酯和衍生肽:合成和活性

噻唑类的氨基酸酯前药，被引入以改善母体药物的药代动力学参数，被证明作为它们的盐是稳定的，但在pH>；5.尽管一些不稳定性是由于简单的水解，但我们发现降解的主要最终产物是通过重排形成的肽。这些肽是稳定的固体：它们保持了显著的抗病毒活性，总体而言，与母体噻唑类化合物相比，它们表现出更好的药代动力学（更好的溶解度和降低的清除率）。我们描述了这些肽的制备和评价。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Bio & Med Chem Au 药物、生物、化学-

CiteScore

4.10

自引率

0.00%

发文量

期刊介绍： ACS Bio & Med Chem Au is a broad scope open access journal which publishes short letters comprehensive articles reviews and perspectives in all aspects of biological and medicinal chemistry. Studies providing fundamental insights or describing novel syntheses as well as clinical or other applications-based work are welcomed.This broad scope includes experimental and theoretical studies on the chemical physical mechanistic and/or structural basis of biological or cell function in all domains of life. It encompasses the fields of chemical biology synthetic biology disease biology cell biology agriculture and food natural products research nucleic acid biology neuroscience structural biology and biophysics.The journal publishes studies that pertain to a broad range of medicinal chemistry including compound design and optimization biological evaluation molecular mechanistic understanding of drug delivery and drug delivery systems imaging agents and pharmacology and translational science of both small and large bioactive molecules. Novel computational cheminformatics and structural studies for the identification (or structure-activity relationship analysis) of bioactive molecules ligands and their targets are also welcome. The journal will consider computational studies applying established computational methods but only in combination with novel and original experimental data (e.g. in cases where new compounds have been designed and tested).Also included in the scope of the journal are articles relating to infectious diseases research on pathogens host-pathogen interactions therapeutics diagnostics vaccines drug-delivery systems and other biomedical technology development pertaining to infectious diseases.