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- Title
Repurposing Synthetic Acetaminophen Derivatives Containing a Benzothiazole Scaffold as an Alternative Therapy for Infectious Diarrhea Caused by Drug-Resistant Shigella Species.
- Authors
Pone Kamdem, Boniface; Pinlap, Brice Rostan; Noumboue Kouamou, Bijou-Lafortune; Youbi Kamche, Aubin; Kuate, Boris Arnaud; Tsemeugne, Joseph; Ngomo, Orleans; Mkounga, Pierre; Fekam Boyom, Fabrice
- Abstract
Diarrhea remains one of the leading causes of mortality worldwide, especially among children. Accumulated evidence has shown that Shigella species are the most prevalent bacteria responsible for diarrhea in developing countries. Antimicrobial therapy is necessary for Shigella infections; however, the development of resistance against current drugs justifies the pressing need to search for alternative medications. In this study, we have applied antibacterial phenotypic screening to identify potent anti-Shigella compounds across a broad chemical diversity, including selected acetaminophen derivatives containing a benzothiazole backbone, and their combination with certain antibiotics. As a result, two acetaminophen derivatives containing a benzothiazole backbone (4a and 4b) inhibited the growth of Shigella flexneri with a common MIC value of 12.5 µg/mL. These compounds were established through a time-kill kinetics study to be potentially bactericidal. Meanwhile, the 2-aminobenzothiazoles (1a and 1b) used for the synthesis of compounds 4 (a and b) were found to be poorly active (MIC: 100 µg/mL) against this pathogen. Combination studies of 4a and 4b with the least effective antibiotics (ceftriaxone and cotrimoxazole) demonstrated synergistic anti-Shigella activity with MIC values decreasing from 12.5 to 0.781 μg/ mL. The present study demonstrates that the azobenzothiazole dyes 4 (a and b) can be repurposed as potential anti-Shigella compounds, thus providing potential chemical pharmacophores for the discovery of drugs against infectious diarrhea caused by Shigella and other enteric pathogens, especially in developing countries.
- Subjects
DIARRHEA; ACETAMINOPHEN; BENZOTHIAZOLE; ALTERNATIVE medicine; SHIGELLA; DRUG resistance in bacteria
- Publication
Future Pharmacology, 2024, Vol 4, Issue 2, p420
- ISSN
2673-9879
- Publication type
Article
- DOI
10.3390/futurepharmacol4020023