AI Article Synopsis
- * The thioacid-modified NSAIDs demonstrate enhanced cyclooxygenase inhibition, potentially with better effectiveness, and avoid unnecessary structural changes, ensuring only the intended active ingredients are released.
- * The design takes advantage of how esterases can efficiently break down thiocarboxylic acids for controlled HS release, and the study supports its concept through synthesis, kinetics assessment, pharmacological testing, and evaluations on toxicity and gut microbiota in animal models.
Article Abstract
Efforts to synergize hydrogen sulfide (HS) with NSAIDs have faced challenges due to complex structural entities and independent release kinetics. This study presents a highly atom-efficient approach of using a thiocarboxylic acid (thioacid) as a novel HS releasing precursor and successfully employs it to modify NSAIDs, which offers several critical advantages. First, thioacid-modified NSAID is active in inhibiting cyclooxygenase, sometimes with improved potency. Second, this prodrug approach avoids introducing extra structural moieties, allowing for the release of only the intended active principals. Third, the release of HS and NSAID is concomitant, thus optimally synchronizing the concentration profiles of the two active principals. The design is based on our discovery that esterases can directly and efficiently hydrolyze thiocarboxylic acids, enabling controlled release HS. This study demonstrates the proof of principle through synthesizing analogs, assesses release kinetics, enzyme inhibition, and pharmacological efficacy, and evaluates toxicity and gut microbiota regulation in animal models.
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| http://dx.doi.org/10.1021/acs.jmedchem.4c01254 | DOI Listing |
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Article Synopsis
- * The thioacid-modified NSAIDs demonstrate enhanced cyclooxygenase inhibition, potentially with better effectiveness, and avoid unnecessary structural changes, ensuring only the intended active ingredients are released.
- * The design takes advantage of how esterases can efficiently break down thiocarboxylic acids for controlled HS release, and the study supports its concept through synthesis, kinetics assessment, pharmacological testing, and evaluations on toxicity and gut microbiota in animal models.
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