Multicomponent synthesis of 4,4-dimethyl sterol analogues and their effect on eukaryotic cells

Most sterols, such as cholesterol and ergosterol, become functional only after the removal of the two methyl groups at C-4 from their biosynthetic precursors. Nevertheless, some findings suggest that 4,4-dimethyl sterols might be involved in specific physiological processes. In this paper we present...

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Autor principal: Alonso, F.
Otros Autores: Cirigliano, A.M, Dávola, M.E, Cabrera, G.M, García Liñares, G.E, Labriola, C., Barquero, A.A, Ramírez, Javier Alberto
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: Elsevier Inc. 2014
Acceso en línea:Registro en Scopus
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024 7 |2 cas  |a Sterols 
030 |a STEDA 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
100 1 |a Alonso, F. 
245 1 0 |a Multicomponent synthesis of 4,4-dimethyl sterol analogues and their effect on eukaryotic cells 
260 |b Elsevier Inc.  |c 2014 
270 1 0 |m Ramírez, J.A.; Departamento de Química Orgánica and UMYMFOR, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 3, C1428EGA Buenos Aires, Argentina; email: jar@qo.fcen.uba.ar 
504 |a Patterson, W.G., Phylogenetic distribution of sterols (1994) Isopentenoids and Other Natural Products, 562 VOL., pp. 5-90. , W.D. Nes, American Chemical Society 
504 |a Nes, W.D., Patterson, G.W., (1991) Physiology and Biochemistry of Sterols, , The American Oil Chemists Society 
504 |a Nes, W.D., Biosynthesis of cholesterol and other sterols (2011) Chem Rev, 111, pp. 6423-6451 
504 |a Rahier, A., Dissecting the sterol C-4 demethylation process in higher plants. from structures and genes to catalytic mechanism (2011) Steroids, 76, pp. 340-352 
504 |a Byskov, A.G., Andersen, C.Y., Nordholm, L., Thøgersen, H., Xia, G., Wassmann, O., Chemical structure of sterols that activate oocyte meiosis (1995) Nature, 374, pp. 559-562 
504 |a Hughes, A.L., Lee, C.-Y.S., Bien, C.M., Espenshade, P.J., 4-Methyl sterols regulate fission yeast SREBP-Scap under low oxygen and cell stress (2007) Journal of Biological Chemistry, 282 (33), pp. 24388-24396. , http://www.jbc.org/cgi/reprint/282/33/24388, DOI 10.1074/jbc.M701326200 
504 |a Hirota, M., Mori, T., Yoshida, M., Iiye, R., Suppression of tumor promoter-induced inflammation of mouse ear by ursolic acid and 4,4-dimethylcholestane derivatives (1990) Agric Biol Chem, 54, pp. 1073-1075 
504 |a Dávola, M.E., Alonso, F., Cabrera, G.M., Ramírez, J.A., Barquero, A.A., Sterol analogues with diamide side chains interfere with the intracellular localization of viral glycoproteins (2012) Biochem Biophys Res Commun, 427, pp. 107-112 
504 |a Alonso, F., Cirigliano, A.M., Cabrera, G.M., Ramírez, J.A., Synthesis and preliminary biological screening of sterol analogues as new antifungal agents against plant pathogens (2010) Steroids, 75, pp. 659-664 
504 |a Sandoval, A., Thomas, G.H., Djerassi, C., Rosenkranz, G., Sondheimer, F., Steroids. LXI. Synthesis of 19-nor-desoxycorticosterone, a potent mineralocorticoid hormone (1954) J Am Chem Soc, 77, pp. 148-151 
504 |a Fei, X.-S., Tian, W.-S., Chen, Q.-Y., Synthesis of 4-trifluoromethylsteroids: A novel class of steroid 5α-reductase inhibitors (1997) Bioorganic and Medicinal Chemistry Letters, 7 (24), pp. 3113-3118. , DOI 10.1016/S0960-894X(97)10156-1, PII S0960894X97101561 
504 |a Hadacek, F., Greger, H., Testing of antifungal natural products: Methodologies, comparability of results and assay choice (2000) Phytochemical Analysis, 11 (3), pp. 137-147. , DOI 10.1002/(SICI)1099-1565(200005/06)11:3<137::AID-PCA514>3.0. CO;2-I 
504 |a Kueng, W., Silber, E., Eppenberger, U., Quantification of cells cultured on 96-well plates (1989) Analytical Biochemistry, 182 (1), pp. 16-19 
504 |a Zhu, J., Bienaymé, H., (2006) Multicomponent Reactions, , Wiley 
504 |a Zhang, N., O'Donnell, K., Sutton, D.A., Nalim, F.A., Summerbell, R.C., Padhye, A.A., Members of the Fusarium solani species complex that cause infections in both humans and plants are common in the environment (2006) J Clin Microbiol, 44, pp. 2186-2190 
504 |a Rassi, Jr.A., Rassi, A., Marin-Neto. Chagas disease (2010) Lancet, 375, pp. 1388-1402 
506 |2 openaire  |e Política editorial 
520 3 |a Most sterols, such as cholesterol and ergosterol, become functional only after the removal of the two methyl groups at C-4 from their biosynthetic precursors. Nevertheless, some findings suggest that 4,4-dimethyl sterols might be involved in specific physiological processes. In this paper we present the synthesis of a collection of analogues of 4,4-dimethyl sterols with a diamide side chain and a preliminary analysis of their in vitro activity on selected biological systems. The key step for the synthesis involves an Ugi condensation, a versatile multicomponent reaction. Some of the new compounds showed antifungal and cytotoxic activity. © 2014 Elsevier Inc. All rights reserved.  |l eng 
536 |a Detalles de la financiación: Universidad de Buenos Aires, UBACyT X-084 
536 |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas, PIP 0315 
536 |a Detalles de la financiación: This work was supported by grants from Universidad de Buenos Aires (UBACyT X-084) and CONICET (PIP 0315). We are grateful to UMYMFOR (UBA-CONICET) for the analytical and spectroscopic determinations. Appendix A 
593 |a Departamento de Química Orgánica and UMYMFOR, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 3, C1428EGA Buenos Aires, Argentina 
593 |a Departamento de Química Biológica and IQUIBICEN, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 4, C1428EGA Buenos Aires, Argentina 
593 |a Laboratorio de Glicobilogía, Fundación Instituto Leloir e Instituto de Investigaciones Bioquímicas de Buenos Aires, Avenida Patricias Argentinas 435, C1405BWE Buenos Aires, Argentina 
690 1 0 |a 4,4-DIMETHYL STEROLS 
690 1 0 |a ANTIFUNGAL 
690 1 0 |a CYTOTOXIC 
690 1 0 |a KEYWORDS 
690 1 0 |a UGI REACTION 
690 1 0 |a (17BETA) 4,4 DIMETHYL 3 OXOANDROST 5 ENE 17 CARBOXYLATE 
690 1 0 |a (17BETA) 4,4 DIMETHYL 3 OXOANDROST 5 ENE 17 CARBOXYLIC ACID 
690 1 0 |a (17BETA) N ((T BUTYLCARBAMOYL)METHYL) N (2 CHLOROPHENYL) 4,4 DIMETHYL 3 HYDROXYANDROST 5 ENE 17 CARBOXAMIDE 
690 1 0 |a (17BETA) N ((T BUTYLCARBAMOYL)METHYL) N (2 ETHYL 6 METHYLPHENYL) 4,4 DIMETHYL 3 OXOANDROST 5 ENE 17 CARBOXAMIDE 
690 1 0 |a (17BETA) N ((T BUTYLCARBAMOYL)METHYL) N (2 FLUOROPHENYL) 4,4 DIMETHYL 3 OXOANDROST 5 ENE 17 CARBOXAMIDE 
690 1 0 |a (17BETA) N ((T BUTYLCARBAMOYL)METHYL) N (2 NAPHTHYL) 4,4 DIMETHYL 3 OXOANDROST 5 ENE 17 CARBOXAMIDE 
690 1 0 |a (17BETA) N ((T BUTYLCARBAMOYL)METHYL) N (4 CHLOROPHENYL) 4,4 DIMETHYL 3 HYDROXYANDROST 5 ENE 17 CARBOXAMIDE 
690 1 0 |a (17BETA) N ((T BUTYLCARBAMOYL)METHYL) N (4 CHLOROPHENYL) 4,4 DIMETHYL 3 OXOANDROST 5 ENE 17 CARBOXAMIDE 
690 1 0 |a (17BETA) N ((T BUTYLCARBAMOYL)METHYL) N (4 FLUOROPHENYL) 4,4 DIMETHYL 3 HYDROXYANDROST 5 ENE 17 CARBOXAMIDE 
690 1 0 |a (17BETA) N ((T BUTYLCARBAMOYL)METHYL) N (4 FLUOROPHENYL) 4,4 DIMETHYL 3 OXOANDROST 5 ENE 17 CARBOXAMIDE 
690 1 0 |a (17BETA) N ((T BUTYLCARBAMOYL)METHYL) N (4 METHOXYPHENYL) 4,4 DIMETHYL 3 HYDROXYANDROST 5 ENE 17 CARBOXAMIDE 
690 1 0 |a (17BETA) N ((T BUTYLCARBAMOYL)METHYL) N (4 METHOXYPHENYL) 4,4 DIMETHYL 3 OXOANDROST 5 ENE 17 CARBOXAMIDE 
690 1 0 |a (17BETA) N ((T BUTYLCARBAMOYL)METHYL) N (4 METHYLPHENYL) 4,4 DIMETHYL 3 HYDROXYANDROST 5 ENE 17 CARBOXAMIDE 
690 1 0 |a (17BETA) N ((T BUTYLCARBAMOYL)METHYL) N PHENYL 4,4 DIMETHYL 3 HYDROXYANDROST 5 ENE 17 CARBOXAMIDE 
690 1 0 |a (17BETA) N ((T BUTYLCARBAMOYL)METHYL) N PHENYL 4,4 DIMETHYL 3 OXOANDROST 5 ENE 17 CARBOXAMIDE 
690 1 0 |a 2 (T BUTYLAMINO) 2 OXOETHYL (17BETA) 4,4 DIMETHYL 3 HYDROXYANDROST 5 ENE 17 CARBOXYLATE 
690 1 0 |a ANTIFUNGAL AGENT 
690 1 0 |a STEROL DERIVATIVE 
690 1 0 |a UNCLASSIFIED DRUG 
690 1 0 |a STEROL 
690 1 0 |a ANTIFUNGAL ACTIVITY 
690 1 0 |a ARTICLE 
690 1 0 |a BROTH DILUTION 
690 1 0 |a DRUG CYTOTOXICITY 
690 1 0 |a DRUG SYNTHESIS 
690 1 0 |a EUKARYOTIC CELL 
690 1 0 |a FUSARIUM 
690 1 0 |a MINIMUM INHIBITORY CONCENTRATION 
690 1 0 |a NONHUMAN 
690 1 0 |a STRUCTURE ACTIVITY RELATION 
690 1 0 |a TRYPANOSOMA CRUZI 
690 1 0 |a ANIMAL 
690 1 0 |a BIOSYNTHESIS 
690 1 0 |a CHEMISTRY 
690 1 0 |a CHLOROCEBUS AETHIOPS 
690 1 0 |a DRUG EFFECTS 
690 1 0 |a ELECTROSPRAY MASS SPECTROMETRY 
690 1 0 |a EUKARYOTIC CELL 
690 1 0 |a HUMAN 
690 1 0 |a NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY 
690 1 0 |a VERO CELL LINE 
690 1 0 |a ANIMALS 
690 1 0 |a CERCOPITHECUS AETHIOPS 
690 1 0 |a EUKARYOTIC CELLS 
690 1 0 |a HUMANS 
690 1 0 |a MAGNETIC RESONANCE SPECTROSCOPY 
690 1 0 |a SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION 
690 1 0 |a STEROLS 
690 1 0 |a VERO CELLS 
700 1 |a Cirigliano, A.M. 
700 1 |a Dávola, M.E. 
700 1 |a Cabrera, G.M. 
700 1 |a García Liñares, G.E. 
700 1 |a Labriola, C. 
700 1 |a Barquero, A.A. 
700 1 |a Ramírez, Javier Alberto 
773 0 |d Elsevier Inc., 2014  |g v. 84  |h pp. 1-6  |p Steroids  |x 0039128X  |w (AR-BaUEN)CENRE-577  |t Steroids 
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