RESUMO
BACKGROUND: A non-hazardous synthetic methodology has been developed for the preparation of compounds based on indolofuroquinoxaline framework. Lemon juice that is known to play the role of a biocatalyst in various organic reactions was used for this purpose. METHOD: A number of indolofuroquinoxaline derivatives were prepared via the lemon juice mediated condensation of methyl 2-(2-chloro-1H-indol-3-yl)-2-oxoacetate or its N-alkyl derivatives with 1,2- diamines under ultrasound irradiation. All the synthesized compounds were screened via an MTT assay for their potential anticancer properties in vitro using a number of cancer cell lines including MDA-MB 231, and MCF7, K562, Colo-205 and IMR-32 and the non-cancerous HEK293 cell line. Compounds 3a, 3b and 3c showed promising growth inhibition against K562, MDA-MB 231 and MCF7 cell lines but no significant effects on HEK293 cell line suggesting their selectivity towards cancer cells. RESULTS AND CONCLUSION: Moreover, according to their IC50 values, all these compounds appeared to be relatively more potent towards K562 cell line over MDA-MB 231 and MCF7 cell lines indicating their potential against leukemia.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Citrus , Sucos de Frutas e Vegetais , Quinoxalinas/síntese química , Quinoxalinas/farmacologia , Ondas Ultrassônicas , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HEK293 , Humanos , Concentração Inibidora 50 , Espectrometria de Massas , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
BACKGROUND: The 3,4-diyne substituted isocoumarins have been designed, synthesized and explored as potential anti-proliferative agents. METHOD: Ultrasound assisted synthesis of these compounds was carried out by using a three-step method involving (i) Pd/C-Cu catalyzed cross-coupling between the methyl 2-iodobenzoate and buta- 1,3-diynylbenzene followed by (ii) I2-mediated electrophilic cyclization of the resultant 2-(alk-1- ynyl)benzoate ester and (iii) subsequent alkynylation of 4-iodo-3-(phenylethynyl)-isocoumarin under Pd/C-Cu catalysis. CONCLUSION: The synthesized compounds showed promising growth inhibition when tested against MDA-MB 231 and K562 cancer cell lines.
Assuntos
Antineoplásicos/farmacologia , Citotoxinas/farmacologia , Di-Inos/farmacologia , Isocumarinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/síntese química , Citotoxinas/química , Di-Inos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isocumarinas/síntese química , Isocumarinas/química , Relação Estrutura-AtividadeRESUMO
BACKGROUND: SnCl2·2H2O has been used as a convenient precatalyst for the one-pot and rapid synthesis of 2-substituted quinolines under ultrasound irradiation in water. The reaction involved a 3-component reaction of aniline, aldehydes, and ethyl 3,3-diethoxypropionate in the presence of aerial oxygen to give the desired products in good yields. CONCLUSION: Several of these compounds showed antibacterial activities when tested against gram-positive and gram-negative species. One compound i.e. 4b showed promising activities across both the species.
Assuntos
Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Quinolinas/farmacologia , Compostos de Estanho/química , Ondas Ultrassônicas , Antibacterianos/síntese química , Antibacterianos/química , Catálise , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Quinolinas/síntese química , Quinolinas/química , Relação Estrutura-Atividade , Água/químicaRESUMO
BACKGROUND: 3-Methyleneisoindolin-1-one derivatives containing a pyridin-2-ylmethyl substituent on their ring nitrogen were designed as potential bioactive agents. A one-pot synthesis of these compounds was achieved via sequential C-C coupling, followed by C-Si bond cleavage and subsequent tandem C-C/C-N bond forming reaction under ultrasound irradiation. METHOD: The methodology involved coupling of (trimethylsilyl)acetylene with iodoarenes in the presence of 10% Pd/C-CuI-PPh3-Et3N in MeOH followed by treating the reaction mixture with K2CO3 in aqueous MeOH, and finally coupling with 2-iodo-N-(pyridin-2-ylmethyl)benzamide. The in vitro evaluation of these compounds was performed to identify some initial hit molecules one of which showed dose dependent inhibition of PDE4B.
Assuntos
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Isoindóis/farmacologia , Inibidores da Fosfodiesterase 4/farmacologia , Ondas Ultrassônicas , Animais , Linhagem Celular , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/isolamento & purificação , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Isoindóis/síntese química , Isoindóis/química , Inibidores da Fosfodiesterase 4/síntese química , Inibidores da Fosfodiesterase 4/química , Células Sf9 , Spodoptera , Relação Estrutura-AtividadeRESUMO
A number of 2H-1,3-benzoxazin-4(3H)-one derivatives containing indole or benzofuran moieties were synthesized by using Pd/C-Cu mediated coupling-cyclization strategy as a key step. The o-iodoanilides or o-iodophenol were coupled with 3-{2-(prop-2-ynyloxy)ethyl}-2H-benzo[e][1,3]oxazin-4(3H)-one using 10%Pd/C-CuI-PPh3 as a catalyst system and Et3N as a base to give the target compounds. All the synthesized compounds were tested for their PDE4B inhibitory potential in vitro using a cell based cAMP reporter assay. Some of them showed fold increase of the cAMP level when tested at 30 µM. A representative compound showed encouraging PDE4B inhibitory properties that were supported by its docking results.