Evaluation of the inhibition of angiotensin-converting enzyme by new thiomorpholine compounds using capillary zone electrophoresis
DOI:
https://doi.org/10.29356/jmcs.v62i3.453Keywords:
Angiotensin Converting Enzyme, Capillary Zone Electrophoresis, Captopril, Hippuric Acid, InhibitionAbstract
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 inhibición de la enzima convertidora de angiotensina (ACE) se determinó 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 fármaco es utilizado como agente antihipertensivo y conocido por su efecto biológico sobre la ACE. El estudio se realizó utilizando la técnica de electroforesis capilar, con una reacción en línea utilizando hippuril-histidil-leucina (HHL) como sustrato para producir ácido hipúrico (HA). El HA se detectó a 254 nm, que es la longitud de onda de detección para obtener la cuantificación de este compuesto. Eso se realizó bajo las condiciones experimentales reportadas para tal interacción. A partir de esto, se calculó la movilidad electroforética del ácido hipúrico para deducir el tiempo efectivo de migración y la cantidad recuperada, esto para probar y cuantificar la actividad en línea de la enzima.
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