RESUMO
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 inâ vitro antimalarial activity test was conducted for each compound against P. falciparum K1. The IC50 values ranged from 5.56 to 25.65â µM. A cytotoxicity profile of the compounds at 200â 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.
Assuntos
Antimaláricos , Malária , Humanos , Antimaláricos/química , Simulação de Acoplamento Molecular , beta-Lactamas/farmacologia , beta-Lactamas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Triazóis/química , Acetatos , Relação Estrutura-AtividadeRESUMO
In the title mol-ecule, C(15)H(14)N(2)O(4), the dihedral angle between the two benzene rings is 29.52â (8)°. The nitro and two meth-oxy substituents are almost coplanar with their respective benzene rings. The crystal structure is stabilized by inter-molecular C-Hâ¯O inter-actions.
RESUMO
The title compound, C(15)H(14)N(2)O(4), has two crystallographically independent mol-ecules in the asymmetric unit. In both mol-ecules, the nitro and the two meth-oxy substituents are coplanar with the benzene rings to which they are attached. The benzene rings are nearly coplanar, with dihedral angles between the two benzene rings of 10.39â (8) and 5.95â (8)° in the two mol-ecules. The two independent mol-ecules in the asymmetric unit are rotated with respect to each other such that the dihedral angles between equivalent benzene rings are 49.11â (8) and 63.93â (8)°. In the crystal structure, inter-molecular C-Hâ¯O hydrogen-bond contacts and a weak C-Hâ¯π inter-action are observed.