Effect of Antibiotic Amphotericin B Combinations with Selected 1,3,4-Thiadiazole Derivatives on RPTECs in an In Vitro Model

• Published in: International journal of molecular sciences 2022-12, Vol.23 (23), p.15260
• Main Authors: Dróżdż, Agnieszka, Sławińska-Brych, Adrianna, Kubera, Dominika, Kimsa-Dudek, Magdalena, Gola, Joanna Magdalena, Adamska, Jolanta, Kruszniewska-Rajs, Celina, Matwijczuk, Arkadiusz, Karcz, Dariusz, Dąbrowski, Wojciech, Stepulak, Andrzej, Gagoś, Mariusz
• Format: Article
• Language: English
• Subjects: 1,3,4-thiadiazole derivatives; Amphotericin B; Amphotericin B - pharmacology; Anti-Bacterial Agents; Antibiotics; Antifungal activity; Antifungal agents; Antifungal Agents - pharmacology; Apoptosis; Benzene; caspase activity; Caspase-2; cell apoptosis; Cell death; Cell viability; Clinical medicine; Cytotoxicity; Dehydrogenases; Drug dosages; Enzyme-linked immunosorbent assay; Epithelial Cells; Epithelium; Evaluation; Flow cytometry; Fungicides; Homeostasis; Humans; Oxidants; Oxidative stress; Oxidizing agents; Reactive oxygen species; RPTEC model; Spectrum analysis; Thiadiazoles; Thiadiazoles - pharmacology
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232315260

4-(5-methyl-1,3,4-thiadiazole-2-yl) benzene-1,3-diol (C1) and 4-[5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-yl] benzene1,3-diol (NTBD) are representative derivatives of the thiadiazole group, with a high antimycotic potential and minimal toxicity against normal human fibroblast cells. The present study has proved its ability to synergize with the antifungal activity of AmB. The aim of this work was to evaluate the cytotoxic effects of C1 or NTBD, alone or in combination with AmB, on human renal proximal tubule epithelial cells (RPTECs) in vitro. Cell viability was assessed with the MTT assay. Flow cytometry and spectrofluorimetric techniques were used to assess the type of cell death and production of reactive oxygen species (ROS), respectively. The ELISA assay was performed to measure the caspase-2, -3, and -9 activity. ATR-FTIR spectroscopy was used to evaluate biomolecular changes in RPTECs induced by the tested formulas. The combinations of C1/NTBD and AmB did not exert a strong inhibitory effect on the viability/growth of kidney cells, as evidenced by the negligible changes in the apoptotic/necrotic rate and caspase activity, compared to the control cells. Both NTBD and C1 displayed stronger anti-oxidant activity when combined with AmB. The relatively low nephrotoxicity of the thiadiazole derivative combinations and the protective activity against AmB-induced oxidative stress may indicate their potential use in the therapy of fungal infections.