RESUMO
4-Chloro-3-({[(substitutedamino)carbonothioyl]amino}sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide (1-20) and 4-chloro-3-({[3-(substituted)-4-oxo-1,3-thiazolidine-2-ylidene]amino}sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide derivatives (21-31) were synthesized from 4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3-sulfamoylbenzamide (indapamide). 4-Chloro-3-({[(4-chlorophenyl) amino) carbonothioyl]amino}sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide 12 demonstrated the highest proapoptotic activity among all synthesized compounds on melanoma cell lines MDA-MB-435 with 3.7% growth inhibition at the concentration of 10 µM. Compound 12 (SGK 266) was evaluated in vitro using the MTT colorimetric method against melanoma cancer cell line MDA-MB435 growth inhibition for different doses and exhibited anticancer activity with IC50 values of 85-95 µM against melanoma cancer cell line MDA-MB435. In addition, this compound was investigated as inhibitors of four physiologically relevant human carbonic anhydrase isoforms, hCA I, II, IX and XII. The compund inhibited these enzymes with IC50 values ranging between 0.72 and 1.60 µM.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/farmacologia , Indapamida/análogos & derivados , Indapamida/farmacologia , Antineoplásicos/química , Inibidores da Anidrase Carbônica/química , Anidrases Carbônicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colorimetria , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indapamida/síntese química , Indapamida/química , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
A series of N-(4-chloro-3-sulfamoylbenzamido)-1,2,3,4-tetrahydroquinoline++ + (IV-1) and isoquinoline (IV-2) have been synthesized and their diuretic and antihypertensive activities evaluated. While none of the test compounds was found to be provided with antihypertensive properties, most of them displayed a diuretic activity comparable to (IV-2 a) or higher (IV-1 a,b) (IV-2 c) than those of indapamide and clopamide, taken as reference drugs.
Assuntos
Diuréticos/síntese química , Indapamida/síntese química , Isoquinolinas/síntese química , Sulfonamidas/síntese química , Animais , Anti-Hipertensivos/síntese química , Pressão Sanguínea/efeitos dos fármacos , Fenômenos Químicos , Química , Clopamida/farmacologia , Diurese/efeitos dos fármacos , Diuréticos/farmacologia , Indapamida/análogos & derivados , Isoquinolinas/farmacologia , Espectroscopia de Ressonância Magnética , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos , Sulfonamidas/farmacologiaRESUMO
In pursuing earlier studies, the synthesis of a series of 1 and 1,3- substituted 2-(4-chloro-3-sulfamoylbenzamido)isoindolines (V a-e), related to indapamide, is described. These compounds were evaluated for diuretic and antihypertensive activities.
