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

Victor Hugo Vazquez-Valadez, Ivonne Carrillo Cedillo, Nayeli Ramírez Carreño, Ana María Velázquez-S, Víctor H. Abrego Reyes, Rafael López Castañares, Enrique Angeles

Abstract


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.


Keywords


Angiotensin Converting Enzyme; Capillary Zone Electrophoresis; Captopril; Hippuric Acid; Inhibition

Full Text:

PDF

References


White, J.S., White, D.C., (Eds.), Source Book of Enzymes, CRC Press, New York, 1997, p. 516-528.

Beneteau-Burnat, B., Baudin, B. Crit. Rev. Clin. Lab. Sci. 1991, 28, 337-357.

Lieberman, J., Rea, T.H., Ann. Intern. Med. 1977, 87, 422-425. DOI 10.7326/0003-4819-87-4-422

Cushman, D.W., Ondetti, M.A., Biochem. Pharmacol.1980, 29, 1871-1877 DOI: 10.1016/0006-2952(80)90096-9

Bünning, P., J. Card. Pharmacol. 1987, 10, S28-S31.

Cushman, D.W., Cheung, H.S., Biochem. Pharmacol. 1971, 20, 1637-1648. DOI:10.1016/0006-2952(71)90292-9

Schnaith, E., Beyrau, R., Bückner, B., Klein, R.M., Rick, W., Clin. Chim. Acta 227 1994, 145-158 DOI: 10.1016/0009-8981(94)90143-0

Friedland, J., Silverstein, E., Am. J. Clin. Pathol. 1976, 66, 416-424. DOI:10.1093/ajcp/66.2.416

Ryan, J.W., Chung, A., Ammons, C., Carlton, M.L., A simple radioassay for angiotensin-converting enzyme Biochem. J. 1977, 167, 501-504. DOI:10.1042/bj1670501

Ryder, K.W., Thompson, H., Smith, D., Sample, M., Sample, R.B., Oei, T.O., Clin. Biochem. 1984, 17, 302-305. DOI:10.1016/S0009-9120(84)90601-5

Vázquez-Valadez, V. H., Abrego, V.H., Martínez, P.A. , Torres, G., Zúñiga, O., Escutia, D., Vilchis, R., Velázquez, A.M., Martínez, L., Ruiz, M., Camacho, B., López-Castañares, R., Angeles, E., Open Med Chem J. 2013, 7, 30–38. DOI:10.2174/1874104501307010030

Chiknas, S.G., Clin. Chem. 1979, 25, 1259-1262.[PubMed]

Neels, H.M., Scharpe, S.L., Van Sande, M.E., Verkerk, R.M., Van Acker, K.J., Clin. Chem. 1982, 28, 1352-1355.

Meng, Q.C., Balcells, E., Dell’italia, D., Durand, D., Oparil, S., Biochem. Pharmacol, 1995, 50, 1445-1450. DOI:10.1016/0006-2952(95)02038-1

Van Dyck S, Vissers S, Van Schepdael A, Hoogmartens J Chromatogr A. 2003 Feb 7;986(2):303-311. DOI:10.1016/S0021-9673(02)01995-7

Shihabi, Z.K., J. Chromatogr. 1999, A 853, 185-188. DOI:10.1016/S0021-9673(99)00474-4

Zhang, R.Z., Xu, X.H., Chen, T.B., Li, L., Rao, P.F., Anal. Biochem. 2000, 280, 286-290. DOI:10.1006/abio.2000.4535

Bao, J., Regnier, F.E., J. Chromatogr. 1992, 608, 217-224. DOI:10.1016/0021-9673(92)87127-T

Miller, K.J., Leesong, I.K., Bao, J.M., Regnier, F.E., Lytle, F.E., Anal. Chem. 65 (1993) 3267-3270. DOI: 10.1021/ac00070a017

Wu, D., Regnier, F.E., Linhares, M.C., J. Chromatogr. 1994, B 657, 357-363. DOI:10.1016/0378-4347(94)00140-5

Bao, J.J., Fujima, J.M., Danielson, N.D., J. Chromatogr. 1997, B 699, 481-497. DOI:10.1016/S0378-4347(96)00244-7

Watanabe, T., Yamamoto, A., Nagai, S., Terabe, S., Electrophoresis 1998, 19, 2331-2337. DOI:10.1002/elps.1150191313

Saevels, J., Van Schepdael, A., Hoogmartens, J., Electrophoresis 1996, 17, 1222-1227. DOI:10.1002/elps.1150170709

Van Dyck, A., Van Schepdael, A., Hoogmartens, J., Electrophoresis 2001, 22, 1436-1442. 10.1002/1522-2683(200105)22:7<1436::AID-ELPS1436>3.0.CO;2-8

Van Dyck, S., Van Schepdael, A., Hoogmartens, J., Electrophoresis 2002, 23, 2854-2859. https://doi.org/10.1002/1522-2683(200209)23:17<2854::AID-ELPS2854>3.0.CO;2-Y

Saevels, J., Van den Steen, K., Van Schepdael, A., Hoogmartens, J., J. Chromatogr. 1996, A 745, 293-298.

Whisnant, A.R., Johnston, S.E., Gilman, S.D., Electrophoresis 2000, 21, 1341-1348. https://doi.org/10.1002/(SICI)1522-2683(20000401)21:7<1341::AID-ELPS1341>3.0.CO;2-9

Taga, A., Honda, S., J. Chromatogr. 1996, A 742, 243-250. DOI:10.1016/0021-9673(96)00250-6

Stout, D. M., Matier, W. L., Barcelon,Y.C., Reynolds, R. D., Brown, B. S. J. Med. Chem. 1983 26, 808 – 813. DOI: 10.1021/jm00360a005

Stout, D. M., Matier, W. L., Barcelon,Y.C., Reynolds, R. D., Brown, B. S. J. Med. Chem. 1984 27, 1347 – 1350. DOI: 10.1021/jm00376a022

Stout, D. M., Matier, W. L., Barcelon,Y.C., Reynolds, R. D., Brown, B. S. 1985 J. Med. Chem. 28(3), 295-298. DOI: 10.1021/jm00381a006

Velázquez, A. Ma., Torres, L. A., Díaz, G., Ramírez, A., Hernández, R., Santillán, H., Martínez, L., Martínez, I., Díaz-Barriga, S., Ábrego, V., Balboa, M. A., Camacho, B., López Castañares, R., Dueñas-González, A., Cabrera, G., Angeles, E. Arkivok. 2006, ii, 150-161. DOI:10.3998/ark.5550190.0007.218

Martinez Aguilar, L., Velazquez Sanchez, A.M., Diaz-Barriga Arceo, S., Romero Rojas, A., Posada Galarza, M.E.R., Angeles, E., (Universidad Nacional Autonoma de Mexico, Mex.). Mex. Pat. Appl. (2007), CODEN: MXXXA3 MX 2005PA12635 A 20070522. Application: MX 2005-12635 20051123 Title 298633 2012.




DOI: http://dx.doi.org/10.29356/jmcs.v62i3.453

Refbacks

  • There are currently no refbacks.


Copyright (c) 2019 Victor Hugo Vazquez-Valadez, Ivonne Carrillo Cedillo, Nayeli Ramírez Carreño, Ana María Velázquez-S, Víctor Abrego Reyes, Rafael López Castañares, Enrique Angeles

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Journal of the Mexican Chemical Society (J. Mex. Chem. Soc.) Vol 62, No 2 (2018). Quarterly publication (April-June). Edited and distributed by Sociedad Química de México, A.C. Barranca del Muerto 26, Col. Crédito Constructor, Del. Benito Juárez, C.P. 03940, Mexico City. Phone: +5255 56626837; +5255 56626823 Contact: soquimex@sqm.org.mx http://www.sqm.org.mx Editor-in-Chief: Ignacio González-Martínez. Indexed Journal. Certificate of reserved rights for recurrent publications under digital distribution granted by the Instituto Nacional del Derecho de Autor (INDAUTOR): 04-2018-091118040000-203. Certificate of lawful title and content: Under procedure. ISSN-e granted by the Instituto Nacional del Derecho de Autor (INDAUTOR): 2594-0317. ISSN granted by the Instituto Nacional del Derecho de Autor (INDAUTOR): 1870-249X. Postal registration of printed matter deposited by editors or agents granted by SEPOMEX: IM09-0312 Copyright © Sociedad Química de México, A.C. Total or partial reproduction is prohibited without written permission of the right holder. The Figures/schemes quality and the general contents of this publication are full responsibility of the authors. Updated December 12th, 2018 by Adriana Vázquez (editorial assistant, e-mail: editor.jmcs@gmail.com), J. Mex. Chem. Soc., Sociedad Química de México, A.C.