Imidazole and nitroimidazole derivatives as NADH-fumarate reductase inhibitors Density functional theory studies, homology modeling, and molecular docking

Imidazole and nitroimidazole derivatives as NADH-fumarate reductase inhibitors : Density functional theory studies, homology modeling, and molecular docking

© 2022 The Authors. Journal of Computational Chemistry published by Wiley Periodicals LLC.

Bibliographische Detailangaben
Veröffentlicht in:Journal of computational chemistry. - 1984. - 43(2022), 23 vom: 05. Sept., Seite 1573-1595
1. Verfasser: Campos-Fernández, Linda (VerfasserIn)
Weitere Verfasser: Ortiz-Muñiz, Rocío, Cortés-Barberena, Edith, Mares-Sámano, Sergio, Garduño-Juárez, Ramón, Soriano-Correa, Catalina
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2022
Zugriff auf das übergeordnete Werk:Journal of computational chemistry
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Chagas disease DFT calculations NADH-fumarate reductase homology modeling molecular docking Enzyme Inhibitors Imidazoles Nitroimidazoles mehr... NAD 0U46U6E8UK Oxidoreductases Acting on CH-CH Group Donors EC 1.3.- fumarate reductase (NADH) EC 1.3.1.6
Beschreibung
Zusammenfassung:© 2022 The Authors. Journal of Computational Chemistry published by Wiley Periodicals LLC.
Chagas disease is caused by Trypanosoma cruzi. Benznidazole and nifurtimox are drugs used for its therapy; nevertheless, they have collateral effects. NADH-fumarate (FUM) reductase is a potential pharmacological target since it is essential for survival of parasite and is not found in humans. The objectives are to design and characterize the electronic structure of imidazole and nitroimidazole derivatives at DFT-M06-2X level in aqueous solution; also, to model the NADH-FUM reductase and analyze its intermolecular interactions by molecular docking. Quantum-chemical descriptors allowed to select the molecules with the best physicochemical properties and lowest toxicity. A high-quality three-dimensional structure of NADH-FUM reductase was obtained by homology modeling. Water molecules do not have influence in the interaction between FUM and NADH-FUM reductase. The main hydrogen-binding interactions for FUM were identified in NADH, Lys172, and Arg89; while hydrophobic interactions in Phe479, Thr174, Met63. The molecules S3-8, S2-8, and S1-8 could be inhibitors of NADH-FUM reductase
Beschreibung:Date Completed 27.07.2022
Date Revised 29.09.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1096-987X
DOI:10.1002/jcc.26959