Volume: 4, 2025
4th International PhD Student’s Conference at the University of Life Sciences in Lublin, Poland:
ENVIRONMENT – PLANT – ANIMAL – PRODUCT
Abstract number: H023
DOI: https://doi.org/10.24326/ICDSUPL4.H023
Published online: 9 April 2025
ICDSUPL, 4, H023 (2025)
Exploring the synergy between 1,3,4-thiadiazole derivative and amphotericin B. Spectroscopic and biological evidence
Lidia Ślusarczyk1*, Michaela Murzyniec2, Mikołaj Gurba2,3, Kamila Rachwał4, Andrzej Gorecki5, James Hooper2, Mariusz Gagoś6, Arkadiusz Matwijczuk1
1 1Department of Biophysics, Faculty of Environmental Biology, University of Life Sciences in Lublin, Akademicka 13, 20-950 Lublin, Poland
2Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Kraków, Poland
3Institute of Advanced Materials, Faculty of Chemistry, Wrocław University of Science and Technology, Wyrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland
4Department of Biotechnology, Microbiology and Human Nutrition, Faculty of Food Science and Biotechnology, University of Life Sciences in Lublin, Skromna 8, 20-704 Lublin, Poland
5 Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland
6 Department of Cell Biology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, Poland
* Corresponding author: lidia.slusarczyk@up.lublin.pl
Abstract
Currently, there is still ongoing research to discover new substances with antifungal properties. A promising approach may be the investigation of synergistic effects between known antifungal antibiotics and other substances. In our research group, we have been searching for years for effective synergistic antifungal systems involving compounds from the 1,3,4-thiadiazole group and known antibiotics. The article presents spectroscopic, theoretical (quantum chemistry calculations), and microbiological studies of a synergistic system between the compound 2,4-dihydroxy-N-(5-methyl-1,3,4-thiadiazol-2-yl) benzothioamide (TBTA) and the polyene antibiotic Amphotericin B (AmB). Spectroscopic studies were conducted using various methods, including electronic absorption and fluorescence spectra measurements, resonance light scattering (RLS) measurements, circular dichroism (CD) spectra, dynamic light scattering (DLS), fluorescence anisotropy measurements, and time-resolved fluorescence lifetime measurements using the single-photon counting method. The studies were carried out in two different environments: in DMSO solvent and in PBS buffer. This system was chosen to facilitate the observation of monomeric, dimeric, and aggregated forms of the antibiotic. Spectroscopic studies revealed differences in the aggregation state of AmB in the buffer system after the addition of TBTA. In particular, partial deaggregation of AmB was observed in RLS spectra measurements. Computational models also provided deeper insight into the interactions between TBTA and AmB, showing that the compound preferentially interacts with the antibiotic in regions where AmB aggregates form, i.e., near hydrophobic regions. Additionally, microbiological studies confirmed the synergy between the molecules and demonstrated that the addition of TBTA allows for a fourfold reduction in the effective inhibitory concentration of AmB in the most efficient synergistic system, containing 0.25 μg/ml of AmB and 16 μg/ml of TBTA. The above research represents the first such detailed analysis of a new 1,3,4-thiadiazole derivative and the “gold standard” in antifungal treatment. These studies will be continued in the future to explore their activity against other fungal organisms and to identify other effective compounds that form efficient synergistic systems with Amphotericin B.
Keywords: synergism (1,3,4-thiadiazole derivative + amphotericin B antibiotic (AmB)), DFTB , molecular spectroscopy (CD, DLS, RLS, and TCSPC, anisotropy)
How to cite
L. Ślusarczyk, M. Murzyniec, M. Gurba, K. Rachwał, A. Gorecki, J. Hooper, M. Gagoś, A. Matwijczuk, 2025. Exploring the synergy between 1,3,4-thiadiazole derivative and amphotericin B. Spectroscopic and biological evidence. In: 4th International PhD Student’s Conference at the University of Life Sciences in Lublin, Poland: Environment – Plant – Animal – Product. https://doi.org/10.24326/ICDSUPL4.H023