RESUMEN
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.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/farmacología , Indapamida/análogos & derivados , Indapamida/farmacología , Antineoplásicos/química , Inhibidores de Anhidrasa Carbónica/química , Anhidrasas Carbónicas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colorimetría , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Indapamida/síntesis química , Indapamida/química , Modelos Moleculares , Estructura Molecular , Relación Estructura-ActividadRESUMEN
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.
Asunto(s)
Diuréticos/síntesis química , Indapamida/síntesis química , Isoquinolinas/síntesis química , Sulfonamidas/síntesis química , Animales , Antihipertensivos/síntesis química , Presión Sanguínea/efectos de los fármacos , Fenómenos Químicos , Química , Clopamida/farmacología , Diuresis/efectos de los fármacos , Diuréticos/farmacología , Indapamida/análogos & derivados , Isoquinolinas/farmacología , Espectroscopía de Resonancia Magnética , Masculino , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas , Sulfonamidas/farmacologíaRESUMEN
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.