RESUMEN
A series of novel benzocoumarin amide derivatives have been synthesized and evaluated for their anti-thrombotic activity. Amongst these, compounds 5, 7 and 8 exhibited promising anti-thrombotic profile in an established model of mouse thrombosis. Hence, comprehensive profiling on platelet aggregation and coagulation parameters was carried out to assess its potential as a lead candidate. In vitro treatment of these compounds in mice plasma resulted into significant reduction in ADP (p<0.01) and collagen (p<0.001) induced platelet aggregation. Moreover, Compounds 5, 7 and 8 also significantly increased thrombin time (p<0.05). Thus, in the present study, these benzocoumarin amide derivatives exhibited anti-thrombotic profile via both anti-platelet as well as anti-coagulant action.
Asunto(s)
Cumarinas/síntesis química , Fibrinolíticos/síntesis química , Adenosina Difosfato/farmacología , Animales , Colágeno/farmacología , Cumarinas/farmacología , Fibrinolíticos/farmacología , Ratones , Inhibidores de Agregación Plaquetaria/síntesis química , Inhibidores de Agregación Plaquetaria/farmacología , Relación Estructura-Actividad , Tiempo de TrombinaRESUMEN
The control of malaria has been complicated with increasing resistance of malarial parasite against existing antimalarials. Herein, we report the synthesis of a new series of chloroquine-chalcone based hybrids (8-22) and their antimalarial efficacy against both chloroquine-susceptible (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. Most of the compounds showed enhanced antimalarial activity as compared to chloroquine in chloroquine-resistant (K1) strain of Plasmodium falciparum. Furthermore, to unfold the mechanism of action of these synthesized hybrid molecules, we carried out hemin dependent studies, in which three compounds were found to be active.
Asunto(s)
Antimaláricos/química , Antimaláricos/farmacología , Chalcona/química , Chalcona/farmacología , Cloroquina/química , Cloroquina/farmacología , Plasmodium falciparum/efectos de los fármacos , Animales , Antimaláricos/síntesis química , Supervivencia Celular/efectos de los fármacos , Chalcona/síntesis química , Chlorocebus aethiops , Cloroquina/síntesis química , Resistencia a Medicamentos , Hemina/metabolismo , Humanos , Malaria Falciparum/tratamiento farmacológico , Células VeroRESUMEN
Molecular hybridization approach is an emerging tool in drug discovery for designing new pharmacophores with biological activity. A novel, new series of coumarin-benzimidazole hybrids were designed, synthesized and evaluated for their broad spectrum antimicrobial activity. Among all the synthesized molecules, compound (E)-3-(2-1H-benzo[d]imidazol-1-yl)-1-((4-chlorobenzyl)oxy)imino)ethyl)-2H-chromen-2-one showed the most promising broad spectrum antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis and Proteus vulgaris. In addition, it has showed no cytotoxicity and hemolysis at 10 times the MIC concentration. SAR studies indicate that position of the chlorine atom in the hybrid critically determines the antibacterial activity.
Asunto(s)
Antibacterianos/farmacología , Antiinfecciosos/farmacología , Bencimidazoles/farmacología , Cumarinas/farmacología , Diseño de Fármacos , Farmacorresistencia Bacteriana Múltiple , Modelos Moleculares , Animales , Antibacterianos/efectos adversos , Antibacterianos/síntesis química , Antibacterianos/química , Antiinfecciosos/efectos adversos , Antiinfecciosos/síntesis química , Antiinfecciosos/química , Bacillus subtilis/efectos de los fármacos , Bacillus subtilis/crecimiento & desarrollo , Bencimidazoles/efectos adversos , Bencimidazoles/síntesis química , Bencimidazoles/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Células del Tejido Conectivo/citología , Células del Tejido Conectivo/efectos de los fármacos , Cumarinas/efectos adversos , Cumarinas/síntesis química , Cumarinas/química , Hemólisis/efectos de los fármacos , Humanos , Hidrocarburos Clorados/efectos adversos , Hidrocarburos Clorados/síntesis química , Hidrocarburos Clorados/química , Hidrocarburos Clorados/farmacología , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Proteus vulgaris/efectos de los fármacos , Proteus vulgaris/crecimiento & desarrollo , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
A series of novel indole-chalcone fibrates were synthesized and their hypolipidemic activity was evaluated in triton WR-1339 induced hyperlipidemic rat model. Preliminary studies indicated that the hybrids 19, 24 and 29 exhibited potent in vitro antioxidant and significant in vivo antidyslipidemic effects. Our results suggest that these new hybrid architectures may serve as promising leads for the development of next generation lipid lowering agents.
Asunto(s)
Antioxidantes/farmacología , Chalcona/farmacología , Diseño de Fármacos , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/farmacología , Indoles/farmacología , Animales , Antioxidantes/síntesis química , Antioxidantes/química , Chalcona/química , Modelos Animales de Enfermedad , Hiperlipidemias/inducido químicamente , Hipolipemiantes/síntesis química , Hipolipemiantes/química , Indoles/química , Lipoproteínas/sangre , Lipoproteínas HDL/sangre , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/sangre , Lipoproteínas LDL/metabolismo , Masculino , Estructura Molecular , Polietilenglicoles/administración & dosificación , RatasRESUMEN
Development of new, targeted antibreast cancer drug which can treat both the hormone receptor (positive and negative) breast cancers is a very challenging task. The concept of molecular hybridization led us to discover a novel class of coumarin-monastrol hybrid, as a novel breast cancer agent which selectively induce apoptosis in both primary and metastatic breast cancer cell lines.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Cumarinas/farmacología , Descubrimiento de Drogas , Pirimidinas/farmacología , Tionas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cumarinas/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Células MCF-7 , Estructura Molecular , Pirimidinas/química , Relación Estructura-Actividad , Tionas/química , Células Tumorales CultivadasRESUMEN
In our continuing search for safe and efficacious antidyslipidemic agents, structurally interesting coumarin-chalcone fibrates were synthesized and evaluated in triton WR-1339 induced hyperlipidemic rats. The most active compound 41 decreased the total cholesterol (TC), phospholipids (PL) and triglycerides (TG), of hyperlipidemic rats by 26, 24, and 25% respectively. In addition, the compound 41 significantly reversed the levels of VLDL, LDL HDL and also increased the LPL activity. Altogether, our data suggests that these novel hybrids would be a potential new class of therapeutic agents against dyslipidemia.
Asunto(s)
Chalconas/farmacología , Cumarinas/farmacología , Dislipidemias/tratamiento farmacológico , Animales , Chalconas/química , Cumarinas/química , Dislipidemias/inducido químicamente , Masculino , Estructura Molecular , Polietilenglicoles , Ratas , Ratas EndogámicasRESUMEN
A novel series of amide based fibrates were synthesized and evaluated for antidyslipidemic activity in triton induced hyperlipidemic rats. Interestingly, the compound 13 produced striking reduction in serum levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG). In addition, it exhibited improved lipoprotein lipase activity and found to possess moderate radical scavenging potential. The results of the above studies shows that the compounds synthesized on fibrate based pharmacophores might result in identification of new lead for dyslipidemia.