Evaluation of Acute and Sub-Acute Toxicity, Oxidative Stress and Molecular Docking of Two Nitrofuranyl Amides as Promising Anti-Tuberculosis Agents
Tuberculosis (TB) remains a widespread infectious disease and one of the top 10 causes of death worldwide. Nevertheless, despite significant advances in the development of new drugs against tuberculosis, many therapies and preventive measures do not lead to the expected favorable health results for...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/8/1174 |
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| author | Simeon Dimitrov Ivaylo Slavchev Rumyana Simeonova Milka Mileva Tania Pencheva Stanislav Philipov Almira Georgieva Elina Tsvetanova Yoanna Teneva Nadezhda Rimpova Georgi Dobrikov Violeta Valcheva |
| author_facet | Simeon Dimitrov Ivaylo Slavchev Rumyana Simeonova Milka Mileva Tania Pencheva Stanislav Philipov Almira Georgieva Elina Tsvetanova Yoanna Teneva Nadezhda Rimpova Georgi Dobrikov Violeta Valcheva |
| author_sort | Simeon Dimitrov |
| collection | DOAJ |
| description | Tuberculosis (TB) remains a widespread infectious disease and one of the top 10 causes of death worldwide. Nevertheless, despite significant advances in the development of new drugs against tuberculosis, many therapies and preventive measures do not lead to the expected favorable health results for various reasons. The aim of this study was to evaluate the acute and sub-acute toxicity and oxidative stress of two selected nitrofuranyl amides with high in vitro antimycobacterial activity. In addition, molecular docking studies were performed on both compounds to elucidate the possibilities for further development of new anti-tuberculosis candidates with improved efficacy, selectivity, and pharmacological parameters. Acute toxicity tests showed that no changes were observed in the skin, coat, eyes, mucous membranes, secretions, and vegetative activity in mice. The histological findings include features consistent with normal histological architecture without being associated with concomitant pathological conditions. The observed oxidative stress markers indicated that the studied compounds disturbed the oxidative balance in the mouse liver. Based on the molecular docking, compound <b>DO-190</b> showed preferable binding energies compared to <b>DO-209</b> in three out of four targets, while both compounds showed promising protein–ligand interactions. Thus, both studied compounds displayed promising activity with low toxicity and can be considered for further evaluation and/or lead optimization. |
| first_indexed | 2024-03-11T00:05:34Z |
| format | Article |
| id | doaj.art-903f4a44d95942858794c0a0543a664f |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T00:05:34Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-903f4a44d95942858794c0a0543a664f2023-11-19T00:23:18ZengMDPI AGBiomolecules2218-273X2023-07-01138117410.3390/biom13081174Evaluation of Acute and Sub-Acute Toxicity, Oxidative Stress and Molecular Docking of Two Nitrofuranyl Amides as Promising Anti-Tuberculosis AgentsSimeon Dimitrov0Ivaylo Slavchev1Rumyana Simeonova2Milka Mileva3Tania Pencheva4Stanislav Philipov5Almira Georgieva6Elina Tsvetanova7Yoanna Teneva8Nadezhda Rimpova9Georgi Dobrikov10Violeta Valcheva11The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaInstitute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaDepartment of Pharmacology, Pharmacotherapy, and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaThe Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaDepartment of Human Anatomy, Histology, General and Clinical Pathology and Forensic Medicine, Faculty of Medicine, Sofia University “St. Kliment Ohridski”, 1407 Sofia, BulgariaThe Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaThe Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaDepartment of Pharmacology, Pharmacotherapy, and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaDepartment of Paediatrics, University Children’s Hospital, Medical University of Sofia, 1431 Sofia, BulgariaInstitute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaThe Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaTuberculosis (TB) remains a widespread infectious disease and one of the top 10 causes of death worldwide. Nevertheless, despite significant advances in the development of new drugs against tuberculosis, many therapies and preventive measures do not lead to the expected favorable health results for various reasons. The aim of this study was to evaluate the acute and sub-acute toxicity and oxidative stress of two selected nitrofuranyl amides with high in vitro antimycobacterial activity. In addition, molecular docking studies were performed on both compounds to elucidate the possibilities for further development of new anti-tuberculosis candidates with improved efficacy, selectivity, and pharmacological parameters. Acute toxicity tests showed that no changes were observed in the skin, coat, eyes, mucous membranes, secretions, and vegetative activity in mice. The histological findings include features consistent with normal histological architecture without being associated with concomitant pathological conditions. The observed oxidative stress markers indicated that the studied compounds disturbed the oxidative balance in the mouse liver. Based on the molecular docking, compound <b>DO-190</b> showed preferable binding energies compared to <b>DO-209</b> in three out of four targets, while both compounds showed promising protein–ligand interactions. Thus, both studied compounds displayed promising activity with low toxicity and can be considered for further evaluation and/or lead optimization.https://www.mdpi.com/2218-273X/13/8/1174nitrofuranyl amidesacute and sub-acute toxicitymarkers of oxidative stressmolecular dockingpathomorphological evaluation |
| spellingShingle | Simeon Dimitrov Ivaylo Slavchev Rumyana Simeonova Milka Mileva Tania Pencheva Stanislav Philipov Almira Georgieva Elina Tsvetanova Yoanna Teneva Nadezhda Rimpova Georgi Dobrikov Violeta Valcheva Evaluation of Acute and Sub-Acute Toxicity, Oxidative Stress and Molecular Docking of Two Nitrofuranyl Amides as Promising Anti-Tuberculosis Agents Biomolecules nitrofuranyl amides acute and sub-acute toxicity markers of oxidative stress molecular docking pathomorphological evaluation |
| title | Evaluation of Acute and Sub-Acute Toxicity, Oxidative Stress and Molecular Docking of Two Nitrofuranyl Amides as Promising Anti-Tuberculosis Agents |
| title_full | Evaluation of Acute and Sub-Acute Toxicity, Oxidative Stress and Molecular Docking of Two Nitrofuranyl Amides as Promising Anti-Tuberculosis Agents |
| title_fullStr | Evaluation of Acute and Sub-Acute Toxicity, Oxidative Stress and Molecular Docking of Two Nitrofuranyl Amides as Promising Anti-Tuberculosis Agents |
| title_full_unstemmed | Evaluation of Acute and Sub-Acute Toxicity, Oxidative Stress and Molecular Docking of Two Nitrofuranyl Amides as Promising Anti-Tuberculosis Agents |
| title_short | Evaluation of Acute and Sub-Acute Toxicity, Oxidative Stress and Molecular Docking of Two Nitrofuranyl Amides as Promising Anti-Tuberculosis Agents |
| title_sort | evaluation of acute and sub acute toxicity oxidative stress and molecular docking of two nitrofuranyl amides as promising anti tuberculosis agents |
| topic | nitrofuranyl amides acute and sub-acute toxicity markers of oxidative stress molecular docking pathomorphological evaluation |
| url | https://www.mdpi.com/2218-273X/13/8/1174 |
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