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Novel Benzotriazole-ß-lactam Derivatives as Antimalarial Agents: Design, Synthesis, Biological Evaluation and Molecular Docking Studies.
Aye, Malihe; Jarrahpour, Aliasghar; Haghighijoo, Zahra; Heiran, Roghayeh; Pournejati, Roya; Karbalaei-Heidari, Hamid Reza; Sinou, Veronique; Brunel, Jean Michel; Akkurt, Mehmet; Özdemir, Namik; Turos, Edward.
Afiliación
  • Aye M; Department of Chemistry, College of Sciences, Shiraz University, Shiraz, 71946-84795, Iran.
  • Jarrahpour A; Department of Civil and Environmental Engineering, Shiraz University, Shiraz, Iran.
  • Haghighijoo Z; Department of Chemistry, College of Sciences, Shiraz University, Shiraz, 71946-84795, Iran.
  • Heiran R; Department of pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
  • Pournejati R; Estahban Higher Education Center- Shiraz University, Estahban, Iran.
  • Karbalaei-Heidari HR; Department of Biology, College of Sciences, Shiraz University, PO Box: 71467-13565, Shiraz, 71454, Iran.
  • Sinou V; Department of Biology, College of Sciences, Shiraz University, PO Box: 71467-13565, Shiraz, 71454, Iran.
  • Brunel JM; Aix Marseille Univ, INSERM, SSA, MCT, Faculté de Pharmacie, 27 bd Jean Moulin, 13385, Marseille, France.
  • Akkurt M; Aix Marseille Univ, INSERM, SSA, MCT, Faculté de Pharmacie, 27 bd Jean Moulin, 13385, Marseille, France.
  • Özdemir N; Department of Physics, Faculty of Sciences, Erciyes University, 38039, Kayseri, Turkey.
  • Turos E; Division of Physics Education, Department of Mathematics and Science Education, Faculty of Education, Ondokuz Mayis University, TR-55139, Samsun, Turkey.
Chem Biodivers ; 21(2): e202301745, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38192127
ABSTRACT
Many people around the world suffer from malaria, especially in tropical or subtropical regions. While malaria medications have shown success in treating malaria, there is still a problem with resistance to these drugs. Herein, we designed and synthesized some structurally novel benzotriazole-ß-lactams using 2-(1H-benzo[d][1,2,3]triazol-1-yl)acetic acid as a key intermediate. To synthesize the target molecules, the ketene-imine cycloaddition reaction was employed. First, The reaction of 1H-benzo[d][1,2,3]triazole with 2-bromoacetic acid in aqueous sodium hydroxide yielded 2-(1H-benzo[d][1,2,3]triazol-1-yl)acetic acid. Then, the treatment of 2-(1H-benzo[d][1,2,3]triazol-1-yl)acetic acid with tosyl chloride, triethyl amine, and Schiff base provided new ß-lactams in good to moderate yields.The formation of all cycloadducts was confirmed by elemental analysis, FT-IR, NMR and mass spectral data. Moreover, X-ray crystallography was used to determine the relative stereochemistry of 4a compound. The in vitro antimalarial activity test was conducted for each compound against P. falciparum K1. The IC50 values ranged from 5.56 to 25.65 µM. A cytotoxicity profile of the compounds at 200 µM final concentration revealed suitable selectivity of the compounds for malaria treatment. Furthermore, the docking study was carried out for each compound into the P. falciparum dihydrofolate reductase enzyme (PfDHFR) binding site to analyze their possible binding orientation in the active site.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Malaria / Antimaláricos Límite: Humans Idioma: En Revista: Chem Biodivers Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Malaria / Antimaláricos Límite: Humans Idioma: En Revista: Chem Biodivers Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Suiza