Effect of Antibiotic Amphotericin B Combinations with Selected 1,3,4-Thiadiazole Derivatives on RPTECs in an In Vitro Model
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...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/15260 |
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| author | Agnieszka Dróżdż Adrianna Sławińska-Brych Dominika Kubera Magdalena Kimsa-Dudek Joanna Magdalena Gola Jolanta Adamska Celina Kruszniewska-Rajs Arkadiusz Matwijczuk Dariusz Karcz Wojciech Dąbrowski Andrzej Stepulak Mariusz Gagoś |
| author_facet | Agnieszka Dróżdż Adrianna Sławińska-Brych Dominika Kubera Magdalena Kimsa-Dudek Joanna Magdalena Gola Jolanta Adamska Celina Kruszniewska-Rajs Arkadiusz Matwijczuk Dariusz Karcz Wojciech Dąbrowski Andrzej Stepulak Mariusz Gagoś |
| author_sort | Agnieszka Dróżdż |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T17:44:41Z |
| format | Article |
| id | doaj.art-9757746e6b3a44229269fab89b7cebd6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:44:41Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9757746e6b3a44229269fab89b7cebd62023-11-24T11:16:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231526010.3390/ijms232315260Effect of Antibiotic Amphotericin B Combinations with Selected 1,3,4-Thiadiazole Derivatives on RPTECs in an In Vitro ModelAgnieszka Dróżdż0Adrianna Sławińska-Brych1Dominika Kubera2Magdalena Kimsa-Dudek3Joanna Magdalena Gola4Jolanta Adamska5Celina Kruszniewska-Rajs6Arkadiusz Matwijczuk7Dariusz Karcz8Wojciech Dąbrowski9Andrzej Stepulak10Mariusz Gagoś11Department of Cell Biology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, PolandDepartment of Cell Biology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, PolandDepartment of Cell Biology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, PolandDepartment of Nutrigenomics and Bromatology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, PolandDepartment of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, PolandDepartment of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, PolandDepartment of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, PolandDepartment of Biophysics, University of Life Sciences, Akademicka 13, 20-950 Lublin, PolandDepartment of Chemical Technology and Environmental Analytics, Cracow University of Technology, 31-155 Krakow, PolandI Clinic of Anaesthesiology and Intensive Therapy with Clinical Paediatric Department, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, PolandDepartment of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, PolandDepartment of Cell Biology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, Poland4-(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.https://www.mdpi.com/1422-0067/23/23/152601,3,4-thiadiazole derivativesamphotericin BRPTEC modelcaspase activitycell viabilitycell apoptosis |
| spellingShingle | Agnieszka Dróżdż Adrianna Sławińska-Brych Dominika Kubera Magdalena Kimsa-Dudek Joanna Magdalena Gola Jolanta Adamska Celina Kruszniewska-Rajs Arkadiusz Matwijczuk Dariusz Karcz Wojciech Dąbrowski Andrzej Stepulak Mariusz Gagoś Effect of Antibiotic Amphotericin B Combinations with Selected 1,3,4-Thiadiazole Derivatives on RPTECs in an In Vitro Model International Journal of Molecular Sciences 1,3,4-thiadiazole derivatives amphotericin B RPTEC model caspase activity cell viability cell apoptosis |
| title | Effect of Antibiotic Amphotericin B Combinations with Selected 1,3,4-Thiadiazole Derivatives on RPTECs in an In Vitro Model |
| title_full | Effect of Antibiotic Amphotericin B Combinations with Selected 1,3,4-Thiadiazole Derivatives on RPTECs in an In Vitro Model |
| title_fullStr | Effect of Antibiotic Amphotericin B Combinations with Selected 1,3,4-Thiadiazole Derivatives on RPTECs in an In Vitro Model |
| title_full_unstemmed | Effect of Antibiotic Amphotericin B Combinations with Selected 1,3,4-Thiadiazole Derivatives on RPTECs in an In Vitro Model |
| title_short | Effect of Antibiotic Amphotericin B Combinations with Selected 1,3,4-Thiadiazole Derivatives on RPTECs in an In Vitro Model |
| title_sort | effect of antibiotic amphotericin b combinations with selected 1 3 4 thiadiazole derivatives on rptecs in an in vitro model |
| topic | 1,3,4-thiadiazole derivatives amphotericin B RPTEC model caspase activity cell viability cell apoptosis |
| url | https://www.mdpi.com/1422-0067/23/23/15260 |
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