RESUMO
A new class of pyrazolo[4,3-c]quinoline (5a-i, 7a-b) and pyrano[3,2-c]quinoline (9a-i) derivatives were designed and synthesized in moderate to good yields by microwave conditions. To enhance the yield of pyrano[3,2-c]quinoline derivatives, multicomponent one-pot synthesis has been developed. The synthesized compounds were identified by spectral and elemental analyses. Compounds 9a and 9i showed good antibacterial activity against Gram-positive and Gram-negative bacterial strains. All of the new compounds exhibited weak to moderate antioxidant activity, compound 9d exerted significant antioxidant power. The cytotoxicity of these compounds were also evaluated against MCF-7 (breast) and A549 (Lung) cancer cell lines. Most of the compounds displayed moderate to good cytotoxic activity against these cell lines. Compound 9i was found to be significantly active in this assay and also induced cell death by apoptosis. Molecular docking studies were carried out using EGFR inhibitor in order to determine the molecular interactions.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Nitroquinolinas/farmacologia , Células A549 , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Compostos de Bifenilo/química , Domínio Catalítico , Receptores ErbB/química , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Química Verde , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular , Nitroquinolinas/síntese química , Nitroquinolinas/química , Picratos/química , Piranos/síntese química , Piranos/química , Piranos/farmacologia , Pirazóis/síntese química , Pirazóis/química , Pirazóis/farmacologia , Relação Estrutura-AtividadeRESUMO
A series of 4-quinolone-3-carboxylic acid-containing spirooxindole-pyrrolidine derivatives was synthesized via multicomponent 1,3-dipolar cycloaddition reactions of azomethine ylides with new (E)-4-oxo-6-(3-phenyl-acryloyl)-1,4-dihydroquinoline-3-carboxylic acids in good yields with high regioselectivity. The cycloadducts were characterized by analytical and spectral data including [Formula: see text], [Formula: see text], 2D NMR and mass spectroscopy. The structure of one of the compounds (8a) was investigated theoretically by computational techniques. DFT studies support the proposed mechanism for this cycloaddition reaction. Furthermore, antibacterial activities of the new compounds were evaluated against Gram-positive and Gram-negative bacterial strains. Compounds 8f, 8m and 8p showed potent inhibition activities against selected bacteria. The in vitro cytotoxicity of spirooxindole derivatives (8a-r) was evaluated against MCF-7 breast cancer cell line. Among the various compounds tested, compound 8f [Formula: see text] showed significant cytotoxic activity compared to the standard drug doxorubicin [Formula: see text].
