RESUMO
A simple, highly efficient and environmentally friendly microwave accelerated one-pot synthesis of a series of differently substituted bis-azetidinones have been synthesized expeditiously in good yields from 1,2-diaminoethane and aromatic aldehydes in the presence of zeolite. The structures of the newly synthesized compounds were confirmed by IR, NMR, and mass spectra. The design and calculated molecular properties of all the reported compounds are on the basis of hypothetical antibacterial pharmacophores, which were formulated to interact with microorganisms. A correlation of structure and activity relationship of these compounds with respect to Lipinski rules and drug likeness properties of drugs are described and verified experimentally.
Assuntos
Anti-Infecciosos/síntese química , Antídotos/química , Azetidinas/síntese química , Bentonita/química , Desenho de Fármacos , Iminas/síntese química , Aldeídos/química , Anti-Infecciosos/análise , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Azetidinas/análise , Azetidinas/química , Azetidinas/farmacologia , Fenômenos Químicos , Etilenodiaminas/química , Etilenos/química , Iminas/química , Cetonas/química , Testes de Sensibilidade Microbiana , Micro-Ondas , Terapia de Alvo Molecular , Relação Quantitativa Estrutura-AtividadeRESUMO
A novel series of 6-(2-chloroquinolin-3-yl)-4-substituted-phenyl-6H-1,3-oxazin-2-amines were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive (MRC-02) as well as chloroquine resistant (RKL9) strains of Plasmodium falciparum. The activity tested was at nanomolar concentration. ß-Hematin formation inhibition activity (BHIA(50)) of oxazines were determined and correlated with antimalarial activity. A reasonably good correlation (r = 0.49 and 0.51, respectively) was observed between antimalarial activity (IC(50)) and BHIA(50). This suggests that antimalarial mode of action of these compounds seems to be similar to that of chloroquine and involves the inhibition of hemozoin formation. Some of the compounds were showing better antimalarial activity than chloroquine against resistant strain of P. falciparum and were also found to be active in the in vivo experiment.