Evaluation of the inhibition of angiotensin-converting enzyme by new thiomorpholine compounds using capillary zone electrophoresis

Abstract. The inhibition capacity of the angiotensin converting enzyme (ACE) was determined by 5 different methylthiomorpholine compounds: (4-tert-butyl-2-(thiomorpholin-4-ylmethyl)phenol (LQM318), 4-tert-butyl-2,6-bis(thiomorpholin-4-ylmethyl)phenol (LQM319), 3,5-bis(thiomorpholin-4-ylmethyl) pyrogallol (LQM322), 4-methoxy-2-thiomorpholin-4-ylmethyl-1-phenol (LQM328) and 3,6-bis(thiomorpholin-4-ylmethyl)benzene-1,2-diol (LQM329), using Captopril as a reference. This last drug is used as an antihypertensive agent and known for its biological effect over ACE. The study was done using the capillary electrophoresis technique, with an in-line reaction using hippuryl-histidyl-leucine (HHL) as substrate to produce hippuric acid (HA). HA was detected at 254 nm, which is the detection wavelength to get the quantification of this compound. That was performed under the experimental conditions reported for such interaction. From this, the electrophoretic mobility of hippuric acid was computed in order to deduce the effective migration time and the recovered quantity, to prove and quantify the in-line activity of the enzyme. Resumen. La capacidad de inhibicion de la enzima convertidora de angiotensina (ACE) se determino mediante 5 compuestos diferentes derivados de la metiltiomorfolina: (4-terc-butil-2- (tiomorfolin-4-ilmetil) fenol (LQM318), 4-tert-butil-2,6-bis ( tiomorfolin-4-ilmetil) fenol (LQM319), 3,5-bis (tiomorfolin-4-ilmetil) pirogalol (LQM322), 4-metoxi-2-tiomorfolin-4-ilmetil-1-fenol (LQM328), 3,6 -bis (tiomorfolin-4-ilmetil) benceno-1,2-diol (LQM329) usando como referencia al Captopril. Este farmaco es utilizado como agente antihipertensivo y conocido por su efecto biologico sobre la ACE. El estudio se realizo utilizando la tecnica de electroforesis capilar, con una reaccion en linea utilizando hippuril-histidil-leucina (HHL) como sustrato para producir acido hipurico (HA). El HA se detecto a 254 nm, que es la longitud de onda de deteccion para obtener la cuantificacion de este compuesto. Eso se realizo bajo las condiciones experimentales reportadas para tal interaccion. A partir de esto, se calculo la movilidad electroforetica del acido hipurico para deducir el tiempo efectivo de migracion y la cantidad recuperada, esto para probar y cuantificar la actividad en linea de la enzima.