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Abstract:

Disodium 2β,3α-dihydroxy-5α-cholestan-6-one disulfate (8) has been synthesized using cholesterol (1) as starting material. Sulfation was performed using trimethylamine-sulfur trioxide complex in dimethylformamide as the sulfating agent. The acetylcholinesterase inhibitory activity of compound 8 was evaluated and compared to that of disodium 2β,3α-dihydroxy- 5α-cholestane disulfate (10) and diols 7 and 9. Compounds 8 and 10 were active with IC50 values of 14.59 and 59.65 μM, respectively. Diols 7 and 9 showed no inhibitory activity (IC50 > 500 μM). © 2011 Elsevier Inc. All rights reserved.

Registro:

Documento: Artículo
Título:Synthesis and acetylcholinesterase inhibitory activity of 2β,3α-disulfoxy-5α-cholestan-6-one
Autor:Richmond, V.; Santos, G.A.G.; Murray, A.P.; Maier, M.S.
Filiación:Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Ciudad Universitaria, 1428 Buenos Aires, Argentina
INQUISUR, Departamento de Química, Universidad Nacional Del sur, Avda. Alem 1253, 8000 Bahía Blanca, Buenos Aires, Argentina
Palabras clave:Acetylcholinesterase activity; Sulfated steroids; Synthesis; 2 beta,3 alpha dihydroxy 5 alpha cholestane disulfate; acetylcholinesterase; cholesterol; cholesterol mesylate; cholinesterase inhibitor; disodium 2 beta,3 alpha dihydroxy 5 alpha cholestan 6 one disulfate; n,n dimethylformamide; oxide; sulfur trioxide; trimethylamine; unclassified drug; article; drug activity; drug sulfation; drug synthesis; enzyme activity; enzyme inhibition; IC 50; in vitro study; Acetylcholinesterase; Enzyme Activation; Kinetics; Magnetic Resonance Spectroscopy; Steroids
Año:2011
Volumen:76
Número:10-11
Página de inicio:1160
Página de fin:1165
DOI: http://dx.doi.org/10.1016/j.steroids.2011.05.005
Título revista:Steroids
Título revista abreviado:Steroids
ISSN:0039128X
CODEN:STEDA
CAS:acetylcholinesterase, 9000-81-1; cholesterol, 57-88-5; n,n dimethylformamide, 68-12-2; oxide, 16833-27-5; sulfur trioxide, 7446-11-9; trimethylamine, 75-50-3; Acetylcholinesterase, 3.1.1.7; Steroids
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0039128X_v76_n10-11_p1160_Richmond

Referencias:

  • Kerr, R.G., Baker, B.J., Marine sterols (1991) Nat Prod Rep, 8, pp. 456-497
  • Dauria, M.V., Minale, L., Riccio, R., Polyoxygenated ateroids of marine origin (1993) Chem Rev, 93, pp. 1839-1895
  • Sarma, N.S., Sri Rama Krishna, M., Ramakrishna Rao, S., Sterol ring system oxidation pattern in marine sponges (2005) Marine Drugs, 3 (3), pp. 84-111. , http://www.mdpi.net/marinedrugs/papers/md303084.pdf
  • Digirolamo, J.A., Li, X.-C., Jacob, M.R., Clark, A.M., Ferreira, D., Reversal of fluconazole resistance by sulfated sterols from the marine sponge Topsentia sp (2009) J Nat Prod, 72, pp. 1524-1528
  • McKee, T.C., Cardellina II, J.H., Riccio, R., D'Auria, M.V., Iorizzi, M., Minale, L., Moran, R.A., Boyd, M.R., HIV-inhibitory natural products. 11. Comparative studies of sulfated sterols from marine invertebrates (1994) Journal of Medicinal Chemistry, 37 (6), pp. 793-797
  • Fu, X., Schmitz, F.J., Lee, R.H., Papkoff, J.S., Slate, D.L., Inhibition of protein tyrosine kinase pp60v-src: Sterol sulfates from the brittle star Ophiarachna incrassata (1994) J Nat Prod, 57, pp. 1591-1594
  • Whitson, E.L., Bugni, T.S., Chockalingam, P.S., Concepcion, G.P., Harper, M.K., He, M., Spheciosterol sulfates, PKC-inhibitors from a philippine sponge Spheciospongia sp (2008) J Nat Prod, 71, pp. 1213-1217
  • Comin, M.J., Maier, M.S., Roccatagliata, A.J., Pujol, C.A., Damonte, E.B., Evaluation of the antiviral activity of natural sulfated polyhydroxysteroids and their synthetic derivatives and analogs (1999) Steroids, 64 (5), pp. 335-340. , DOI 10.1016/S0039-128X(99)00016-1, PII S0039128X99000161
  • Rao, M.N., Shinnar, A.E., Noecker, L.A., Chao, T.L., Feibush, B., Snyder, B., Sharkansky, I., Zasloff, M., Aminosterols from the dogfish shark Squalus acanthias (2000) Journal of Natural Products, 63 (5), pp. 631-635. , DOI 10.1021/np990514f
  • Hoye, T.R., Dvornikovs, V., Fine, J.M., Anderson, K.R., Jeffrey, C.S., Muddiman, D.C., Shao, F., Wang, J., Details of the structure determination of the sulfated steroids PSDS and PADS: New components of the sea lamprey (Petromyzon marinus) migratory pheromone (2007) Journal of Organic Chemistry, 72 (20), pp. 7544-7550. , DOI 10.1021/jo070957l
  • Murphy, S., Larrivee, B., Pollet, I., Craig, K.S., Williams, D.E., Huang, X.-H., Abbott, M., Karsan, A., Identification of sokotrasterol sulfate as a novel proangiogenic steroid (2006) Circulation Research, 99 (3), pp. 257-265. , DOI 10.1161/01.RES.0000233316.17882.33, PII 0000301220060804000009
  • Makarieva, T.N., Shubina, L.K., Kalinovsky, A.I., Steroids in porifera. II. Steroid derivatives from two sponges of the family Halichondriidae. Sokotrasterol sulfate, a marine steroid with a new pattern of side chain alkylation (1983) Steroids, 42 (3), pp. 267-281. , DOI 10.1016/0039-128X(83)90039-9
  • Cui, J., Wang, H., Huang, Y., Xin, Y., Zhou, A., Synthesis and cytotoxic analysis of some disodium 3β,6β- dihydroxysterol disulfates (2009) Steroids, 74, pp. 1057-1060
  • Garrido Santos, G.A., Murray, A.P., Pujol, C.A., Damonte, E.B., Maier, M.S., Synthesis and antiviral activity of sulfated and acetylated derivatives of 2β,3α-dihydroxy-5α-cholestane (2003) Steroids, 68 (2), pp. 125-132. , DOI 10.1016/S0039-128X(02)00166-6
  • Rosenberry, T.L., Acetylcholinesterase (1975) Adv Enzymol Relat Areas Mol Biol, 43, pp. 103-218
  • Parle, M., Dhingra, D., Kulkarni, S.K., Neuromodulators of learning and memory (2004) Asia Pacific Journal of Pharmacology, 16 (2), pp. 89-99
  • Enz, A., Amstutz, R., Boddeke, H., Gmelin, G., Malonowski, J., Brain selective inhibition of AChE: A novel approach to therapy for Alzheimers disease (1993) Prog Brain Res, 98, pp. 431-435
  • Langjae, R., Bussarawit, S., Yuenyongsawad, S., Ingkaninan, K., Plubrukarn, A., Acetylcholinesterase-inhibiting steroidal alkaloid from the sponge Corticium sp. (2007) Steroids, 72 (9-10), pp. 682-685. , DOI 10.1016/j.steroids.2007.05.005, PII S0039128X07000906
  • Vela Gurovic, M.S., Castro, M.J., Richmond, V., Faraoni, M.B., Maier, M.S., Murray, A.P., Triterpenoids with acetylcholinesterase inhibition from Chuquiraga erinacea D. Don. Subsp. erinacea (Asteraceae) (2010) Planta Medica, 76, pp. 607-610
  • Ellman, G.L., Courtney, K.D., Andres Jr., V., Featherstone, A new and rapid colorimetric determination of acetylcholinesterase activity (1961) Biochem Pharmacol, 7, pp. 88-95
  • Raves, M.L., Harel, M., Pang, Y.-P., Silman, I., Kozikowski, A.P., Sussman, J.L., Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A (1997) Nature Structural Biology, 4 (1), pp. 57-63. , DOI 10.1038/nsb0197-57
  • Roothaan, C.C.J., (1951) Rev Mod Phys, 23, p. 69
  • Dewar, M.J.S., Zoebisch, E.G., Healy, E.F., Stewart, J.J.P., AM1: A new general purpose quantum mechanical molecular model (1985) J Am Chem Soc, 107, pp. 3902-3909
  • Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M., Cheesemanet, J.R., (2004) Gaussian 03, Revision C.01, , Gaussian, Inc. Wallingford CT
  • Auto-Dock 4.0, The Scripps Research Institute, Department of Molecular Biology, MB-5, La Jolla, CA, 2007; Aburatani, M., Takeuchi, T., Mori, K., A simple synthesis of steroidal 3α,5-cyclo-6-ones and their efficient transformation to steroidal 2-en-6-ones (1987) Synthesis, 1987 (2), pp. 181-183
  • Raghuraman, A., Riaz, M., Hindle, M., Desai, U.R., Rapid and efficient microwave-assisted synthesis of highly sulfated organic scaffolds (2007) Tetrahedron Letters, 48 (38), pp. 6754-6758. , DOI 10.1016/j.tetlet.2007.07.100, PII S0040403907014232
  • Khalid, A., Zaheer-ul-Haq, Anjum, S., Khan, M.R., Atta-ur-Rahman, Choudhary, M.I., Kinetics and structure-activity relationship studies on pregnane-type steroidal alkaloids that inhibit cholinesterases (2004) Bioorganic and Medicinal Chemistry, 12 (9), pp. 1995-2003. , DOI 10.1016/j.bmc.2004.03.002, PII S0968089604001622
  • Zaheer-Ul-Haq, Wellenzohn, B., Liedl, K.R., Rode, B.M., Molecular Docking Studies of Natural Cholinesterase-Inhibiting Steroidal Alkaloids from Sarcococca saligna (2003) Journal of Medicinal Chemistry, 46 (23), pp. 5087-5090

Citas:

---------- APA ----------
Richmond, V., Santos, G.A.G., Murray, A.P. & Maier, M.S. (2011) . Synthesis and acetylcholinesterase inhibitory activity of 2β,3α-disulfoxy-5α-cholestan-6-one. Steroids, 76(10-11), 1160-1165.
http://dx.doi.org/10.1016/j.steroids.2011.05.005
---------- CHICAGO ----------
Richmond, V., Santos, G.A.G., Murray, A.P., Maier, M.S. "Synthesis and acetylcholinesterase inhibitory activity of 2β,3α-disulfoxy-5α-cholestan-6-one" . Steroids 76, no. 10-11 (2011) : 1160-1165.
http://dx.doi.org/10.1016/j.steroids.2011.05.005
---------- MLA ----------
Richmond, V., Santos, G.A.G., Murray, A.P., Maier, M.S. "Synthesis and acetylcholinesterase inhibitory activity of 2β,3α-disulfoxy-5α-cholestan-6-one" . Steroids, vol. 76, no. 10-11, 2011, pp. 1160-1165.
http://dx.doi.org/10.1016/j.steroids.2011.05.005
---------- VANCOUVER ----------
Richmond, V., Santos, G.A.G., Murray, A.P., Maier, M.S. Synthesis and acetylcholinesterase inhibitory activity of 2β,3α-disulfoxy-5α-cholestan-6-one. Steroids. 2011;76(10-11):1160-1165.
http://dx.doi.org/10.1016/j.steroids.2011.05.005