Synthesis and evaluation of the cytotoxic activity of novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1, 2-a]quinoxaline-carboxylate derivatives in myeloid and lymphoid leukemia cell lines (545 views visite)
Eur J Med Chem (ISSN: 0223-5234, 1768-3254, 0223-5234linking), 2016; 113: 214-227.
Export to Esporta in BibTeX Export to Esporta in EndNote
Paper type Tipo di articolo: Journal Article,
Impact factor: 4.519, 5-year impact factor Impact factor a 5 anni: 4.187
Url: https://www2.scopus.com/inward/record.uri?eid=2-s2.0-84959375519&partnerID=40&md5=1dea32a36b6c88eafc5d9f6d11e862df
Keywords Parole chiave: Cancer, Cytotoxic Activity, Leukemia, Pyrrolo[1, 2-A]quinoxaline, Synthesis,
Affiliations Affiliazioni:
*** IBB - CNR ***
Univ. Bordeaux, UFR des Sciences Pharmaceutiques, Cellules Souches Hematopoietiques Normales et Leucemiques, Bordeaux cedex, France
INSERM U1035, Cellules Souches Hématopoïétiques Normales et Leucémiques, Bordeaux, France
INSERM U1212, UMR, CNRS 5320, ARNA Laboratory, Bordeaux, France
Department of Pharmacy, CIRPeB, University of Naples Federico II, Via Mezzocannone, Naples, Italy
Univ. Bordeaux, ISM, CNRS, UMR 5255, 351 cours de la Libération, Talence cedex, France
Univ. Bordeaux, ICMCB, CNRS, UPR 9048, 87, Avenue du Docteur Schweitzer, Pessac cedex, France
Institut de Chimie Organique et Analytique, Univ. Orleans, CNRS, UMR 7311, ICOA, BP 6759, rue de Chartres, Orléans cedex 2, France
Université de Picardie Jules Verne, Laboratoire de Glycochimie, des Antimicrobiens et des Agroressouces, UMR, CNRS 7378, UFR de Pharmacie, 1 rue des Louvels, Amiens cedex 01, France
References Riferimenti:
Lichtman, M.A., Battling the hematological malignancies: the 200 years' war (2008) The Oncologist, 13, pp. 126-13
Campiani, G., Butini, S., Fattorusso, C., Trotta, F., Franceschina, S., De Angelis, M., Nielsen, K.S., Novel Aryl Piperazine Derivatives with Medical Utility (2006)Campiani, G., Aiello, F., Fabbrini, M., Morelli, E., Ramunno, A., Armaroli, S., Nacci, V., Caccia, S., Quinoxalinylethylpyridylthioureas (QXPTs) as potent non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors. Further SAR studies and identification of a novel orally bioavailable hydrazine-based antiviral agent (2001) J. Med. Chem., 44, pp. 305-315
Schann, S., Mayer, S., Gardan, S., Pyrrolo[1,2-a]quinoxaline Derivatives as Adenosine A3 Receptor Modulators and Uses Thereof (2007)Guillon, J., Grellier, P., Labaied, M., Sonnet, P., Léger, J.-M., Déprez-Poulain, R., Forfar-Bares, I., Jarry, C., Synthesis, antimalarial activity and molecular modeling of new pyrrolo[1,2-a]quinoxalines, bispyrrolo[1,2-a]quinoxalines, bispyrido[3,2-e]pyrrolo[1,2-a]pyrazines and bispyrrolo[1,2-a]thieno[3,2-e]pyrazines (2004) J. Med. Chem., 47, pp. 1997-2009
Guillon, J., Forfar, I., Mamani-Matsuda, M., Desplat, V., Saliège, M., Thiolat, D., Massip, S., Mossalayi, D., Synthesis, analytical behaviour and biological evaluation of new 4-substituted pyrrolo[1,2-a]quinoxalines as antileishmanial agents (2007) Bioorg. Med. Chem., 15, pp. 194-210
Guillon, J., Moreau, S., Mouray, E., Sinou, V., Forfar, I., Belisle-Fabre, S., Desplat, V., Grellier, P., New ferrocenic pyrrolo[1,2-a]quinoxaline derivatives: synthesis, and in vitro antimalarial activity (2008) Bioorg. Med. Chem., 16, pp. 9133-9144
Guillon, J., Mouray, E., Moreau, S., Mullié, C., Forfar, I., Desplat, V., Belisle-Fabre, S., Grellier, P., New ferrocenic pyrrolo[1,2-a]quinoxaline derivatives: Synthesis, and in vitro antimalarial activity - part II (2011) Eur. J. Med. Chem., 46, pp. 2310-2326
Ronga, L., Del Favero, M., Cohen, A., Soum, C., Le Pape, P., Savrimoutou, S., Pinaud, N., Guillon, J., Design, synthesis and biological evaluation of novel 4-Alkapolyenylpyrrolo[1,2-a]quinoxalines as antileishmanial agents - part III (2014) Eur. J. Med. Chem., 81, pp. 378-393
Milne, J., Normington, K.D., Milburn, M., Tetrahydroquinoxalinone Sirtuin Modulators (2006)Grande, F., Aiello, F., De Grazia, O., Brizzi, A., Garofalo, A., Meamati, N., Synthesis and antitumor activities of a series of novel quinoxalinhydrazides (2007) Bioorg. Med. Chem., 15, pp. 288-294
Guillon, J., Le Borgne, M., Rimbault, C., Moreau, S., Savrimoutou, S., Pinaud, N., Baratin, S., Jose, J., Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2 (2013) Eur. J. Med. Chem., 65, pp. 205-222
Desplat, V., Geneste, A., Begorre, M.-A., Belisle Fabre, S., Brajot, S., Massip, S., Thiolat, D., Guillon, J., Synthesis of new pyrrolo[1,2-a]quinoxaline derivatives as potential inhibitors of Akt kinase (2008) J. Enzyme Inhib. Med. Chem., 23, pp. 648-658
Desplat, V., Moreau, S., Gay, A., Belisle-Fabre, S., Thiolat, D., Massip, S., Mossalayi, D., Guillon, J., Synthesis and evaluation of the antiproliferative activity of novel pyrrolo[1,2-a]quinoxaline derivatives, potential inhibitors of akt kinase. Part II (2010) J. Enzyme Inhib. Med. Chem., 25, pp. 204-215
Jensen, H.A., Bunaciu, R.P., Varner, J.D., Yen, A., GW5074 and PP2 kinase inhibitors implicate nontraditional c-Raf and Lyn function as drivers of retinoic acid-induced maturation (2015) Cell. Signal, 27, pp. 1666-1675
Kamijo, S., Kanazawa, C., Yamamoto, Y., Copper- or phosphino-catalyzed reaction of alkynes with isocyanides. Regioselective synthesis of substituted pyrroles controlled by the catalyst (2005) J. Am. Chem. Soc., 127, pp. 9260-9266
Gulevich, A.V., Zhdanko, A.G., Orru, R.V.A., Nenajdenko, V.G., Isocyanoacetate derivatives: synthesis, reactivity, and application (2010) Chem. Rev., 110, pp. 5235-5331
Liu, J., Fang, Z., Zhang, Q., Liu, Q., Bi, X., Silver-catalyzed isocyanide-alkyne cycloaddition: a general and practical method to oligosubstituted pyrroles (2013) Angew. Chem. Int. Ed., 52, pp. 6953-6957
Gao, M., He, C., Chen, H., Bai, R., Cheng, B., Lei, A., Synthesis of pyrroles by click reaction: silver-catalyzed cycloaddition of terminal alkynes with isocyanides (2013) Angew. Chem. Int. Ed., 52, pp. 6958-6961
Suzuki, M., Miyoshi, M., Matsumoto, K., Synthesis of amino acids and related compounds. 7. A convenient synthesis of 3-substituted pyrrole-2,4-dicarboxylic acid esters (1974) J. Org. Chem., 39, p. 1980
Guillon, J., Dumoulin, H., Dallemagne, P., Reynolds, R., Rault, S., Synthesis and antituberculosis activity of new phenylpyrrolo[1,2-a]quinoxalinylpyrrole carboxylic acid derivatives (1998) Pharm. Pharmacol. Commun., 4, pp. 33-38
Ngwerume, S., Camp, J.E., Synthesis of highly substituted pyrroles via nucleophilic catalysis (2010) J. Org. Chem., 75, pp. 6271-6274
Trofimov, B.A., Preparation of pyrroles from ketoximes and acetylenes (1999) Adv. Heterocycl. Chem., 51, pp. 177-301
Wang, Y.-F., Toh, K.K., Chiba, S., Narasaka, K., Mn(III)-catalyzed synthesis of pyrroles from vinyl azides and 1,3-dicarbonyl compounds (2008) Org. Lett., 10, pp. 5019-5022
Liu, P., Xu, B., Li, J., Lu, H., LY294002 inhibits leukemia cell invasion and migration through early growth response gene 1 induction independent of phosphatidylinositol 3-kinase-Akt pathway (2008) Biochem. Biophys. Res. Commun., 377, pp. 187-190
Matsuda, S., Nakanishi, A., Wada, Y., Kitagishi, Y., Roles of PI3K/AKT/PTEN pathway as a target for pharmaceutical therapy (2013) Open Med. Chem. J., 7, pp. 23-29
Jørgensen, H.G., Allan, E.K., Graham, S.M., Godden, J.L., Richmond, L., Elliott, M.A., Mountford, J.C., Holyoake, T.L., Lonafarnib reduces the resistance of primitive quiescent CML cells to imatinib mesylate in vitro (2005) Leukemia, 19, pp. 1184-1191
Zhao, S., Konopleva, M., Cabreira-Hansen, M., Xie, Z., Hu, W., Milella, M., Estrov, Z., Andreeff, M., Inhibition of phosphatidylinositol 3-kinase dephosphorylates BAD and promotes apoptosis in myeloid leukemias (2004) Leukemia, 18, pp. 267-275
Lindsley, C.W., The Akt/PKB family of protein kinases: a review of small molecule inhibitors and progress towards target validation: a 2009 update (2010) Curr. Top. Med. Chem., 10, pp. 458-477
Boulahjar, R., Ouach, A., Chiurato, M., Bourg, S., Ravache, M., Le Guével, R., Marionneau-Lambot, S., Routier, S., Novel tetrahydropyrido[1,2-a]isoindolone derivatives (Valmerins): potent cyclin dependant kinase/glycogen synthase kinase 3 inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts (2012) J. Med. Chem., 55, pp. 9589-9606
http://www.molinspiration.com/cgi-bin/properties, Accession date: July 20, 2015Clark, D.E., Pickett, S.D., Computational methods for the prediction of drug likeness (2000) Drug Discov. Today, 5, pp. 49-58
Cardoso, M.F.C., Rodrigues, P.C., Oliveira, M.E.I.M., Gama, I.L., Da Silva, I.M.C.B., Santos, I.O., Rocha, D.R., Paes Silva, F., Jr., Synthesis and evaluation of the cytotoxic activity of 1,2-furanonaphthoquinones tethered to 1,2,3-1H-triazoles in myeloid and lymphoid leukemia cell lines (2014) Eur. J. Med. Chem., 84, pp. 708-717
Bickley, J.F., Gilchrist, T.L., Mendonça, R., Hydroxylation of 1-azabicyclo[4.1.0]hept-3-enes formed by Diels-Alder reactions of benzyl 2H-azirine-3-carboxylate (2002) Arkivoc, 6, pp. 192-204
Supplementary X-ray Crystallographic Data: Cambridge Crystallographic Data Centre, , mailto:deposit@chemcrys.cam.ac.uk, University Chemical Lab, Lensfield Road, Cambridge, CB2 1EW, UK
Sheldrick, G.M., (1996) SADABS, , University of Göttingen Germany
Sheldrick, G.M., (2008) Acta Crystallogr. Sect. A, 64, pp. 112-122
Eur J Med Chem (ISSN: 0223-5234, 1768-3254, 0223-5234linking), 2016; 113: 214-227.
Export to Esporta in BibTeX Export to Esporta in EndNote
Paper type Tipo di articolo: Journal Article,
Impact factor: 4.519, 5-year impact factor Impact factor a 5 anni: 4.187
Url: https://www2.scopus.com/inward/record.uri?eid=2-s2.0-84959375519&partnerID=40&md5=1dea32a36b6c88eafc5d9f6d11e862df
Keywords Parole chiave: Cancer, Cytotoxic Activity, Leukemia, Pyrrolo[1, 2-A]quinoxaline, Synthesis,
Affiliations Affiliazioni:
*** IBB - CNR ***
Univ. Bordeaux, UFR des Sciences Pharmaceutiques, Cellules Souches Hematopoietiques Normales et Leucemiques, Bordeaux cedex, France
INSERM U1035, Cellules Souches Hématopoïétiques Normales et Leucémiques, Bordeaux, France
INSERM U1212, UMR, CNRS 5320, ARNA Laboratory, Bordeaux, France
Department of Pharmacy, CIRPeB, University of Naples Federico II, Via Mezzocannone, Naples, Italy
Univ. Bordeaux, ISM, CNRS, UMR 5255, 351 cours de la Libération, Talence cedex, France
Univ. Bordeaux, ICMCB, CNRS, UPR 9048, 87, Avenue du Docteur Schweitzer, Pessac cedex, France
Institut de Chimie Organique et Analytique, Univ. Orleans, CNRS, UMR 7311, ICOA, BP 6759, rue de Chartres, Orléans cedex 2, France
Université de Picardie Jules Verne, Laboratoire de Glycochimie, des Antimicrobiens et des Agroressouces, UMR, CNRS 7378, UFR de Pharmacie, 1 rue des Louvels, Amiens cedex 01, France
References Riferimenti:
Lichtman, M.A., Battling the hematological malignancies: the 200 years' war (2008) The Oncologist, 13, pp. 126-13
Campiani, G., Butini, S., Fattorusso, C., Trotta, F., Franceschina, S., De Angelis, M., Nielsen, K.S., Novel Aryl Piperazine Derivatives with Medical Utility (2006)Campiani, G., Aiello, F., Fabbrini, M., Morelli, E., Ramunno, A., Armaroli, S., Nacci, V., Caccia, S., Quinoxalinylethylpyridylthioureas (QXPTs) as potent non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors. Further SAR studies and identification of a novel orally bioavailable hydrazine-based antiviral agent (2001) J. Med. Chem., 44, pp. 305-315
Schann, S., Mayer, S., Gardan, S., Pyrrolo[1,2-a]quinoxaline Derivatives as Adenosine A3 Receptor Modulators and Uses Thereof (2007)Guillon, J., Grellier, P., Labaied, M., Sonnet, P., Léger, J.-M., Déprez-Poulain, R., Forfar-Bares, I., Jarry, C., Synthesis, antimalarial activity and molecular modeling of new pyrrolo[1,2-a]quinoxalines, bispyrrolo[1,2-a]quinoxalines, bispyrido[3,2-e]pyrrolo[1,2-a]pyrazines and bispyrrolo[1,2-a]thieno[3,2-e]pyrazines (2004) J. Med. Chem., 47, pp. 1997-2009
Guillon, J., Forfar, I., Mamani-Matsuda, M., Desplat, V., Saliège, M., Thiolat, D., Massip, S., Mossalayi, D., Synthesis, analytical behaviour and biological evaluation of new 4-substituted pyrrolo[1,2-a]quinoxalines as antileishmanial agents (2007) Bioorg. Med. Chem., 15, pp. 194-210
Guillon, J., Moreau, S., Mouray, E., Sinou, V., Forfar, I., Belisle-Fabre, S., Desplat, V., Grellier, P., New ferrocenic pyrrolo[1,2-a]quinoxaline derivatives: synthesis, and in vitro antimalarial activity (2008) Bioorg. Med. Chem., 16, pp. 9133-9144
Guillon, J., Mouray, E., Moreau, S., Mullié, C., Forfar, I., Desplat, V., Belisle-Fabre, S., Grellier, P., New ferrocenic pyrrolo[1,2-a]quinoxaline derivatives: Synthesis, and in vitro antimalarial activity - part II (2011) Eur. J. Med. Chem., 46, pp. 2310-2326
Ronga, L., Del Favero, M., Cohen, A., Soum, C., Le Pape, P., Savrimoutou, S., Pinaud, N., Guillon, J., Design, synthesis and biological evaluation of novel 4-Alkapolyenylpyrrolo[1,2-a]quinoxalines as antileishmanial agents - part III (2014) Eur. J. Med. Chem., 81, pp. 378-393
Milne, J., Normington, K.D., Milburn, M., Tetrahydroquinoxalinone Sirtuin Modulators (2006)Grande, F., Aiello, F., De Grazia, O., Brizzi, A., Garofalo, A., Meamati, N., Synthesis and antitumor activities of a series of novel quinoxalinhydrazides (2007) Bioorg. Med. Chem., 15, pp. 288-294
Guillon, J., Le Borgne, M., Rimbault, C., Moreau, S., Savrimoutou, S., Pinaud, N., Baratin, S., Jose, J., Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2 (2013) Eur. J. Med. Chem., 65, pp. 205-222
Desplat, V., Geneste, A., Begorre, M.-A., Belisle Fabre, S., Brajot, S., Massip, S., Thiolat, D., Guillon, J., Synthesis of new pyrrolo[1,2-a]quinoxaline derivatives as potential inhibitors of Akt kinase (2008) J. Enzyme Inhib. Med. Chem., 23, pp. 648-658
Desplat, V., Moreau, S., Gay, A., Belisle-Fabre, S., Thiolat, D., Massip, S., Mossalayi, D., Guillon, J., Synthesis and evaluation of the antiproliferative activity of novel pyrrolo[1,2-a]quinoxaline derivatives, potential inhibitors of akt kinase. Part II (2010) J. Enzyme Inhib. Med. Chem., 25, pp. 204-215
Jensen, H.A., Bunaciu, R.P., Varner, J.D., Yen, A., GW5074 and PP2 kinase inhibitors implicate nontraditional c-Raf and Lyn function as drivers of retinoic acid-induced maturation (2015) Cell. Signal, 27, pp. 1666-1675
Kamijo, S., Kanazawa, C., Yamamoto, Y., Copper- or phosphino-catalyzed reaction of alkynes with isocyanides. Regioselective synthesis of substituted pyrroles controlled by the catalyst (2005) J. Am. Chem. Soc., 127, pp. 9260-9266
Gulevich, A.V., Zhdanko, A.G., Orru, R.V.A., Nenajdenko, V.G., Isocyanoacetate derivatives: synthesis, reactivity, and application (2010) Chem. Rev., 110, pp. 5235-5331
Liu, J., Fang, Z., Zhang, Q., Liu, Q., Bi, X., Silver-catalyzed isocyanide-alkyne cycloaddition: a general and practical method to oligosubstituted pyrroles (2013) Angew. Chem. Int. Ed., 52, pp. 6953-6957
Gao, M., He, C., Chen, H., Bai, R., Cheng, B., Lei, A., Synthesis of pyrroles by click reaction: silver-catalyzed cycloaddition of terminal alkynes with isocyanides (2013) Angew. Chem. Int. Ed., 52, pp. 6958-6961
Suzuki, M., Miyoshi, M., Matsumoto, K., Synthesis of amino acids and related compounds. 7. A convenient synthesis of 3-substituted pyrrole-2,4-dicarboxylic acid esters (1974) J. Org. Chem., 39, p. 1980
Guillon, J., Dumoulin, H., Dallemagne, P., Reynolds, R., Rault, S., Synthesis and antituberculosis activity of new phenylpyrrolo[1,2-a]quinoxalinylpyrrole carboxylic acid derivatives (1998) Pharm. Pharmacol. Commun., 4, pp. 33-38
Ngwerume, S., Camp, J.E., Synthesis of highly substituted pyrroles via nucleophilic catalysis (2010) J. Org. Chem., 75, pp. 6271-6274
Trofimov, B.A., Preparation of pyrroles from ketoximes and acetylenes (1999) Adv. Heterocycl. Chem., 51, pp. 177-301
Wang, Y.-F., Toh, K.K., Chiba, S., Narasaka, K., Mn(III)-catalyzed synthesis of pyrroles from vinyl azides and 1,3-dicarbonyl compounds (2008) Org. Lett., 10, pp. 5019-5022
Liu, P., Xu, B., Li, J., Lu, H., LY294002 inhibits leukemia cell invasion and migration through early growth response gene 1 induction independent of phosphatidylinositol 3-kinase-Akt pathway (2008) Biochem. Biophys. Res. Commun., 377, pp. 187-190
Matsuda, S., Nakanishi, A., Wada, Y., Kitagishi, Y., Roles of PI3K/AKT/PTEN pathway as a target for pharmaceutical therapy (2013) Open Med. Chem. J., 7, pp. 23-29
Jørgensen, H.G., Allan, E.K., Graham, S.M., Godden, J.L., Richmond, L., Elliott, M.A., Mountford, J.C., Holyoake, T.L., Lonafarnib reduces the resistance of primitive quiescent CML cells to imatinib mesylate in vitro (2005) Leukemia, 19, pp. 1184-1191
Zhao, S., Konopleva, M., Cabreira-Hansen, M., Xie, Z., Hu, W., Milella, M., Estrov, Z., Andreeff, M., Inhibition of phosphatidylinositol 3-kinase dephosphorylates BAD and promotes apoptosis in myeloid leukemias (2004) Leukemia, 18, pp. 267-275
Lindsley, C.W., The Akt/PKB family of protein kinases: a review of small molecule inhibitors and progress towards target validation: a 2009 update (2010) Curr. Top. Med. Chem., 10, pp. 458-477
Boulahjar, R., Ouach, A., Chiurato, M., Bourg, S., Ravache, M., Le Guével, R., Marionneau-Lambot, S., Routier, S., Novel tetrahydropyrido[1,2-a]isoindolone derivatives (Valmerins): potent cyclin dependant kinase/glycogen synthase kinase 3 inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts (2012) J. Med. Chem., 55, pp. 9589-9606
http://www.molinspiration.com/cgi-bin/properties, Accession date: July 20, 2015Clark, D.E., Pickett, S.D., Computational methods for the prediction of drug likeness (2000) Drug Discov. Today, 5, pp. 49-58
Cardoso, M.F.C., Rodrigues, P.C., Oliveira, M.E.I.M., Gama, I.L., Da Silva, I.M.C.B., Santos, I.O., Rocha, D.R., Paes Silva, F., Jr., Synthesis and evaluation of the cytotoxic activity of 1,2-furanonaphthoquinones tethered to 1,2,3-1H-triazoles in myeloid and lymphoid leukemia cell lines (2014) Eur. J. Med. Chem., 84, pp. 708-717
Bickley, J.F., Gilchrist, T.L., Mendonça, R., Hydroxylation of 1-azabicyclo[4.1.0]hept-3-enes formed by Diels-Alder reactions of benzyl 2H-azirine-3-carboxylate (2002) Arkivoc, 6, pp. 192-204
Supplementary X-ray Crystallographic Data: Cambridge Crystallographic Data Centre, , mailto:deposit@chemcrys.cam.ac.uk, University Chemical Lab, Lensfield Road, Cambridge, CB2 1EW, UK
Sheldrick, G.M., (1996) SADABS, , University of Göttingen Germany
Sheldrick, G.M., (2008) Acta Crystallogr. Sect. A, 64, pp. 112-122
Synthesis and evaluation of the cytotoxic activity of novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1, 2-a]quinoxaline-carboxylate derivatives in myeloid and lymphoid leukemia cell lines
Leukemia is the most common blood cancer, and its development starts at diverse points, leading to distinct subtypes that respond differently to therapy. This heterogeneity is rarely taken into account in therapies, so it is still essential to look for new specific drugs for leukemia subtypes or even for therapy-resistant cases. Among heterocyclic compounds that attracted a lot of attention because of its wide spread biological activities, the pyrrolo[1,2-a]quinoxaline heterocyclic framework has been identified as interesting scaffolds for antiproliferative activity against various human cancer cell lines. In the present study, novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1,2-a]quinoxaline-carboxylate derivatives 1a-l have been designed and synthesized. Their cytotoxicities were evaluated against five different leukemia cell lines, including Jurkat and U266 (lymphoid cell lines), and K562, U937, HL60 (myeloid cell lines), as well as normal human peripheral blood mononuclear cells (PBMNCs). Then, apoptosis study was performed with the more interesting compounds. The new pyrrolo[1,2-a]quinoxaline series showed promising cytotoxic potential against all leukemia cell lines tested, and some compounds showed better results than the reference compound A6730. Some compounds, such as 1a, 1e, 1g and 1h are promising because of their high activity against leukemia and their low activity against normal hematopoietic cells. Structure-activity relationships of these new synthetic compounds 1a-l are here also discussed. © 2016 Elsevier Masson SAS. All rights reserved.
Leukemia is the most common blood cancer, and its development starts at diverse points, leading to distinct subtypes that respond differently to therapy. This heterogeneity is rarely taken into account in therapies, so it is still essential to look for new specific drugs for leukemia subtypes or even for therapy-resistant cases. Among heterocyclic compounds that attracted a lot of attention because of its wide spread biological activities, the pyrrolo[1,2-a]quinoxaline heterocyclic framework has been identified as interesting scaffolds for antiproliferative activity against various human cancer cell lines. In the present study, novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1,2-a]quinoxaline-carboxylate derivatives 1a-l have been designed and synthesized. Their cytotoxicities were evaluated against five different leukemia cell lines, including Jurkat and U266 (lymphoid cell lines), and K562, U937, HL60 (myeloid cell lines), as well as normal human peripheral blood mononuclear cells (PBMNCs). Then, apoptosis study was performed with the more interesting compounds. The new pyrrolo[1,2-a]quinoxaline series showed promising cytotoxic potential against all leukemia cell lines tested, and some compounds showed better results than the reference compound A6730. Some compounds, such as 1a, 1e, 1g and 1h are promising because of their high activity against leukemia and their low activity against normal hematopoietic cells. Structure-activity relationships of these new synthetic compounds 1a-l are here also discussed. © 2016 Elsevier Masson SAS. All rights reserved.
Synthesis and evaluation of the cytotoxic activity of novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1, 2-a]quinoxaline-carboxylate derivatives in myeloid and lymphoid leukemia cell lines
No results. Nessun risultato. |
Synthesis and evaluation of the cytotoxic activity of novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1, 2-a]quinoxaline-carboxylate derivatives in myeloid and lymphoid leukemia cell lines
Miceli M, Cutignano A, Conte M, Ummarino R, Romanelli A, Ruvo M, Leone M, Mercurio FA, Doti N, Manzo E, Romano G, Altucci L, Ianora A
* Monoacylglycerides from the Diatom Skeletonema marinoi Induce Selective Cell Death in Cancer Cells (128 visite)
Mar Drugs (ISSN: 1660-3397linking), 2019 Nov 1; 17 (11 ): N/D-N/D.
Impact Factor: 3.345
Dettagli Esporta in BibTeX Esporta in EndNote
Tabbì G, Cassino C, Cavigiolio G, Colangelo D, Ghiglia A, Viano I, Osella D
* Water stability and cytotoxic activity relationship of a series of ferrocenium derivatives. ESR insights on the radical production during the degradation process (531 visite)
J Med Chem (ISSN: 0022-2623, 1520-4804, 0022-2623print), 2002 Dec 19; 45(26): 5786-5796.
Impact Factor: 4.566
Dettagli Esporta in BibTeX Esporta in EndNote
2 Records (2 escludendo Abstract e Conferenze).
Impact factor totale: 7.911 (7.911 escludendo Abstract e Conferenze).
Impact factor a 5 anni totale: 9.535 (9.535 escludendo Abstract e Conferenze).
Vai a fine pagina Versione per copia e incolla facile Esporta tutto in BibTeX Esporta tutto in EndNote
Miceli M, Cutignano A, Conte M, Ummarino R, Romanelli A, Ruvo M, Leone M, Mercurio FA, Doti N, Manzo E, Romano G, Altucci L, Ianora A
* Monoacylglycerides from the Diatom Skeletonema marinoi Induce Selective Cell Death in Cancer Cells (128 visite)
Mar Drugs (ISSN: 1660-3397linking), 2019 Nov 1; 17 (11 ): N/D-N/D.
Impact Factor: 3.345
Dettagli Esporta in BibTeX Esporta in EndNote
Tabbì G, Cassino C, Cavigiolio G, Colangelo D, Ghiglia A, Viano I, Osella D
* Water stability and cytotoxic activity relationship of a series of ferrocenium derivatives. ESR insights on the radical production during the degradation process (531 visite)
J Med Chem (ISSN: 0022-2623, 1520-4804, 0022-2623print), 2002 Dec 19; 45(26): 5786-5796.
Impact Factor: 4.566
Dettagli Esporta in BibTeX Esporta in EndNote
2 Records (2 escludendo Abstract e Conferenze).
Impact factor totale: 7.911 (7.911 escludendo Abstract e Conferenze).
Impact factor a 5 anni totale: 9.535 (9.535 escludendo Abstract e Conferenze).
Last modified by Ultima modifica di Gennaro Angrisano on in data Sunday 12 July 2020, 13:14:47
545 views visite. Last view on Ultima visita in data Wednesday 13 October 2021, 3:34:49
ibb.cnr.it