Ślusarczyk Lidia, Murzyniec Michaela, Gurba Mikołaj, Rachwał Kamila, Górecki Andrzej, Hooper James, Gagoś Mariusz, Matwijczuk Arkadiusz
Department of Biophysics, Faculty of Environmental Biology, University of Life Sciences in Lublin, Akademicka 13, Lublin 20-950, Poland.
Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, Kraków 30-387, Poland.
ACS Omega. 2025 May 22;10(21):21173-21186. doi: 10.1021/acsomega.4c10113. eCollection 2025 Jun 3.
The paper presents the results of an in-depth spectroscopic, theoretical (quantum chemical), and microbiological study conducted on a promising, synergistic composition of a newly considered 1,3,4-thiadiazole derivative, 1,3,4-thiadiazole: 2,4-dihydroxy--(5-methyl-1,3,4-thiadiazol-2-yl)-benzothioamide (TBTA), and the "gold standard" polyene antibiotic, amphotericin B (AmB). The spectroscopic properties of the system were extensively analyzed with a range of spectroscopic measurement techniques, including electronic fluorescence and absorption spectra, resonance light scattering measurements, circular dichroism spectra, dynamic light scattering, and fluorescence anisotropy, which were further complemented with time-resolved measurements of fluorescence lifetimes performed with the single-photon counting method. The samples were prepared in DMSO solutions and/or PBS buffer to facilitate observation of the monomeric, dimeric, and aggregated forms of the antibiotic previously identified in the literature. Absorption and fluorescence emission spectra measured for AmB and the synergistic composition revealed differences that indicated changes in AmB aggregation molecules, particularly in the buffer medium. Together with the results of the other spectroscopic techniques and computations, the effects of AmB disaggregation are clearly observed, and it is seen that TBTA interacts with AmB at the sites where other AmB molecules prefer to interact with it. We also present the first biological analysis of this TBTA/AmB composition, and it confirms the synergistic effects of TBTA. The report provides a detailed description of the synergism observed between a newly synthesized derivative from the group of 1,3,4-thiadiazoles (TBTA) and the antibiotic AmB, an effect that may prove to be very significant in the context of the ongoing efforts to identify new substances with antifungal properties.
本文介绍了一项深入的光谱、理论（量子化学）和微生物学研究结果，该研究针对一种新考虑的1,3,4 - 噻二唑衍生物、1,3,4 - 噻二唑：2,4 - 二羟基 - （5 - 甲基 - 1,3,4 - 噻二唑 - 2 - 基） - 苯并硫代酰胺（TBTA）与“金标准”多烯抗生素两性霉素B（AmB）的有前景的协同组合物进行。利用一系列光谱测量技术对该体系的光谱性质进行了广泛分析，包括电子荧光和吸收光谱、共振光散射测量、圆二色光谱、动态光散射和荧光各向异性，并用单光子计数法进行的荧光寿命时间分辨测量进一步补充。样品在二甲基亚砜溶液和/或磷酸盐缓冲盐溶液中制备，以利于观察文献中先前鉴定的抗生素的单体、二聚体和聚集形式。对AmB和协同组合物测量的吸收和荧光发射光谱显示出差异，表明AmB聚集分子发生了变化，特别是在缓冲介质中。结合其他光谱技术和计算结果，可以清楚地观察到AmB解聚的效果，并且可以看到TBTA在其他AmB分子倾向于与其相互作用的位点与AmB相互作用。我们还展示了这种TBTA/AmB组合物的首次生物学分析，证实了TBTA的协同作用。该报告详细描述了1,3,4 - 噻二唑类新合成衍生物（TBTA）与抗生素AmB之间观察到的协同作用，在正在进行的寻找具有抗真菌特性新物质的努力中，这种作用可能被证明非常重要。
