A New 4-Thiazolidinone Derivative (Les-6490) as a Gut Microbiota Modulator: Antimicrobial and Prebiotic Perspectives

Yulian Konechnyi; Tetyana Rumynska; Ihor Yushyn; Serhii Holota; Vira Turkina; Mariana Ryviuk Rydel; Alicja Sękowska; Yuriy Salyha; Olena Korniychuk; Roman Lesyk

doi:10.3390/antibiotics13040291

A New 4-Thiazolidinone Derivative (Les-6490) as a Gut Microbiota Modulator: Antimicrobial and Prebiotic Perspectives

Antibiotics (Basel). 2024 Mar 22;13(4):291. doi: 10.3390/antibiotics13040291.

Authors

Yulian Konechnyi¹, Tetyana Rumynska^{1

2}, Ihor Yushyn³, Serhii Holota^{3

4}, Vira Turkina^{5

6}, Mariana Ryviuk Rydel^{7

8}, Alicja Sękowska⁹, Yuriy Salyha², Olena Korniychuk¹, Roman Lesyk^{3

10}

Affiliations

¹ Department of Microbiology, Danylo Halytsky Lviv National Medical University, 69 Pekarska St., 79010 Lviv, Ukraine.
² Institute of Animal Biology NAAS, Vasylya Stusa St., 38, 79034 Lviv, Ukraine.
³ Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, 69 Pekarska St., 79010 Lviv, Ukraine.
⁴ Department of Organic and Pharmaceutical Chemistry, Lesya Ukrainka Volyn National University, 13 Volya Ave., 43025 Lutsk, Ukraine.
⁵ Research Institute of Epidemiology and Hygiene, Danylo Halytsky Lviv National Medical University, 69 Pekarska St., 79010 Lviv, Ukraine.
⁶ Department of Biological Chemistry, Danylo Halytsky Lviv National Medical University, 69 Pekarska St., 79010 Lviv, Ukraine.
⁷ Department of Intellectual Property, Information and Corporate Law, Ivan Franko National University of Lviv, 1 Universytetska St., 79000 Lviv, Ukraine.
⁸ Department of Scientific and Medical Information and Intellectual Property, Danylo Halytsky Lviv National Medical University, 69 Pekarska St., 79010 Lviv, Ukraine.
⁹ Microbiology Department, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 9 Maria Skłodowska-Curie St., 85-094 Bydgoszcz, Poland.
¹⁰ Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225 Rzeszow, Poland.

Abstract

A novel 4-thiazolidinone derivative Les-6490 (pyrazol-4-thiazolidinone hybrid) was designed, synthesized, and characterized by spectral data. The compound was screened for its antimicrobial activity against some pathogenic bacteria and fungi and showed activity against Staphylococcus and Saccharomyces cerevisiae (the Minimum Inhibitory Concentration (MIC) 820 μM). The compound was studied in the rat adjuvant arthritis model (Freund's Adjuvant) in vivo. Parietal and fecal microbial composition using 16S rRNA metagenome sequences was checked. We employed a range of analytical techniques, including Taxonomic Profiling (Taxa Analysis), Diversity Metrics (Alpha and Beta Diversity Analysis), Multivariate Statistical Methods (Principal Coordinates Analysis, Principal Component Analysis, Non-Metric Multidimensional Scaling), Clustering Analysis (Unweighted Pair-group Method with Arithmetic Mean), and Comparative Statistical Approaches (Community Differences Analysis, Between Group Variation Analysis, Metastat Analysis). The compound significantly impacted an increasing level of anti-inflammatory microorganisms (Blautia, Faecalibacterium prausnitzii, Succivibrionaceae, and Coriobacteriales) relative recovery of fecal microbiota composition. Anti-Treponemal activity in vivo was also noted. The tested compound Les-6490 has potential prebiotic activity with an indirect anti-inflammatory effect.

Keywords: 4-thiazolidinones; anti-inflammatory activity; antimicrobial activity; gut microbiota; metagenomic sequencing; rats.

Abstract

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