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Evaluation of Acute and Sub-Acute Toxicity, Oxidative Stress and Molecular Docking of Two Nitrofuranyl Amides as Promising Anti-Tuberculosis Agents.
Dimitrov, Simeon; Slavchev, Ivaylo; Simeonova, Rumyana; Mileva, Milka; Pencheva, Tania; Philipov, Stanislav; Georgieva, Almira; Tsvetanova, Elina; Teneva, Yoanna; Rimpova, Nadezhda; Dobrikov, Georgi; Valcheva, Violeta.
Afiliación
  • Dimitrov S; The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
  • Slavchev I; Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
  • Simeonova R; Department of Pharmacology, Pharmacotherapy, and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
  • Mileva M; The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
  • Pencheva T; Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
  • Philipov S; Department of Human Anatomy, Histology, General and Clinical Pathology and Forensic Medicine, Faculty of Medicine, Sofia University "St. Kliment Ohridski", 1407 Sofia, Bulgaria.
  • Georgieva A; The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
  • Tsvetanova E; Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
  • Teneva Y; The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
  • Rimpova N; Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
  • Dobrikov G; Department of Pharmacology, Pharmacotherapy, and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
  • Valcheva V; Department of Paediatrics, University Children's Hospital, Medical University of Sofia, 1431 Sofia, Bulgaria.
Biomolecules ; 13(8)2023 07 28.
Article en En | MEDLINE | ID: mdl-37627241
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 DO-190 showed preferable binding energies compared to DO-209 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Amidas / Antituberculosos Límite: Animals Idioma: En Revista: Biomolecules Año: 2023 Tipo del documento: Article País de afiliación: Bulgaria Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Amidas / Antituberculosos Límite: Animals Idioma: En Revista: Biomolecules Año: 2023 Tipo del documento: Article País de afiliación: Bulgaria Pais de publicación: Suiza