Design, synthesis, and evaluation of novel 6-chloro-/fluorochromone derivatives as potential topoisomerase inhibitor anticancer agents

M.P.S. Ishar, G. Singh, S. Singh, K.K. Sreenivasan

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

6-Chloro-2-pyrrolidino-/morpholino-/piperidino-/N-methylpiperazino-3- formyl-chromones (13-16) and 6-fluoro-2,7-di-morpholino-/piperidino-/N- methylpiperazino-3-formylchromones (17-19) have been synthesized as potential topoisomerase inhibitor anticancer agents, and evaluated, in vitro, against Ehrlich ascites carcinoma (EAC) cells, and also in vivo on EAC bearing mice. The compounds displayed promising anticancer activity under these test systems and shall serve as useful 'leads' for further design. © 2005 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)1366-1370
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number5
DOIs
Publication statusPublished - 2006
Externally publishedYes

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Topoisomerase Inhibitors
Morpholinos
Ascites
Antineoplastic Agents
Bearings (structural)
Chromones
Derivatives
Carcinoma
Cells

Cite this

@article{3946cc41d0954c82b813014c2c6e14b2,
title = "Design, synthesis, and evaluation of novel 6-chloro-/fluorochromone derivatives as potential topoisomerase inhibitor anticancer agents",
abstract = "6-Chloro-2-pyrrolidino-/morpholino-/piperidino-/N-methylpiperazino-3- formyl-chromones (13-16) and 6-fluoro-2,7-di-morpholino-/piperidino-/N- methylpiperazino-3-formylchromones (17-19) have been synthesized as potential topoisomerase inhibitor anticancer agents, and evaluated, in vitro, against Ehrlich ascites carcinoma (EAC) cells, and also in vivo on EAC bearing mice. The compounds displayed promising anticancer activity under these test systems and shall serve as useful 'leads' for further design. {\circledC} 2005 Elsevier Ltd. All rights reserved.",
author = "M.P.S. Ishar and G. Singh and S. Singh and K.K. Sreenivasan",
note = "Cited By :74 Export Date: 10 November 2017 CODEN: BMCLE Correspondence Address: Ishar, M.P.S.; Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143 005, Punjab, India; email: mpsishar@yahoo.com Chemicals/CAS: Antineoplastic Agents; Chromones; DNA Topoisomerases, EC 5.99.1.-; Enzyme Inhibitors References: Champaux, J., (1990) DNA Topology and Its Biological Effects, p. 217. , J.C. Wang N.R. Cozarelli Cold Spring Harbor Laboratory Cold Spring Harbor, NY; Hsieh, T.-S., (1990) DNA Topology and Its Biological Effects, p. 243. , J.C. Wang N.R. Cozarelli Cold Spring Harbor Laboratory Cold Spring Harbor, NY; Caserta, M., Amadei, A., Camilloni, G., Di Mauro, E., (1990) Biochemistry, 29, p. 8152; Harrnon, F.G., Digate, R.J., Kowalczykowski, S.C., (1999) Mol. Cell, 3, p. 611; Nagarajan, M., Morrell, A., Fort, B.C., Meckley, M.R., Antony, S., Kholhagen, G., Pommier, Y., Cushman, M., (2004) J. Med. Chem., 47, p. 5651; Pommier, Y., Tanizawa, A., (1993) Cancer Chemotherapy, p. 214. , J. Hickman T. Tritton Blackwell Scientific Publications Oxford; Chen, A.U., Liu, L.F., (1994) Annu. Rev. Pharmacol. Toxicol., 94, p. 194; Zewail-Foote, M., Hurley, L., (1999) Anti-Cancer Drug Des., 14, p. 1; Levine, C., Hiasa, H., Marians, K.J., (1998) Biochim. Biophys. Acta, 1400, p. 29; Potmesil, M., Kohn, K.K., (1991) Topoisomerases in Cancer, , Oxford University Press: New York, Chapter 2; Osheroff, N., (1989) Pharmacol. Ther., 41, p. 223; Spicer, J., Finlay, G., Baguley, B., Velea, L., Graves, D., Denny, W., (1999) Anti-Cancer Drug Des., 14, p. 37; Gootz, T.D., Birghty, K.E., (1998) The Quinolones, p. 29. , V.T. Andriole 2nd ed. Academic Press San Diego; Hooper, D.C., (2001) Clin. Infect. Dis., 32, p. 9; Fan, J.-Y., Sun, D., Yu, H., Kerwin, S.M., Hurley, L.H., (1995) J. Med. Chem., 38, p. 408; Laco, G.S., Du, W., Kohlhagen, G., Sayer, J.M., Jerina, D.M., Burke, T.G., Curran, D.P., Pommier, Y., (2004) Biorg. Med. Chem., 12, p. 5225; Cianchetta, G., Mannhold, R., Cruciani, G., Baroni, M., Cecchetti, V., (2004) J. Med. Chem., 47, p. 3193; Hsiang, Y.-H., Hertzberg, R., Hecht, S., Liu, L.F., (1985) J. Biol. Chem., 260, p. 14873; Mhaske, S.B., Argade, N.P., (2004) J. Org. Chem., 69, p. 4563; Nagarajan, M., Xiao, X., Antony, S., Kohlhagen, G., Pommier, Y., Cushman, M., (2003) J. Med. Chem., 46, p. 5712; Wall, M.E., (1998) Med. Res. Rev., 18, p. 299; Cragg, G.M., Newman, D.J., (2004) J. Nat. Prod., 67, p. 232; Osheroff, N., Zechiedrich, E.L., Gale, K.C., (1991) BioEssays, 13, p. 269; Rahier, N.J., Eisenhauer, B.M., Gao, R., Jones, S.H., Shannon, R.G., Hecht, S.M., (2004) Org. Lett., 6, p. 321; Arimondo, P., Boukarim, C., Bailly, C., Dauzonne, D., Monneret, C., (2000) Anti-Cancer Drug Des., 15, p. 413; Xiao, Z., Vance, J.R., Bastow, K.F., Brossi, A., Wang, H.-K., Lee, K.-H., (2004) Bioorg. Med. Chem. Lett., 12, p. 3363; Cassady, J.M., Baird, W.M., Chang, C.J., (1990) J. Nat. Prod., 53, p. 23; Kupchan, S.M., Streelman, D.R., Sneden, A.T., (1980) J. Nat. Prod., 43, p. 296; Kim, M.Y., Na, Y., Vankayalapati, H., Gleason-Guzman, M., (2003) J. Med. Chem., 46, p. 2958; Kwok, Y., Sun, D., Clement, J., Hurley, L., (1999) Anti-Cancer Drug Des., 14, p. 443; Domagala, J.M., (1994) J. Antimicrob. Chemother., 33, p. 685; Bryskier, A., Chantot, J.-F., (1995) Drugs, 49 (SUPPL. 2), p. 16; Gootz, T.D., Brighty, K.E., (1996) Med. Res. Rev., 16, p. 433; Xia, Y., Yang, Z.-Y., Xia, P., Hackl, T., Hamel, E., Mauger, A., Wu, J.-H., Lee, K.-H., (2001) J. Med. Chem., 44, p. 3932; Ishar, M.P.S., Kumar, K., Singh, R., (1998) Tetrahedron Lett., 39, p. 6547; Singh, G., Singh, R., Girdhar, N.K., Ishar, M.P.S., (2002) Tetraherdon, 58, p. 2471; Singh, G., Singh, L., Ishar, M.P.S., (2002) Tetraherdon, 58, p. 7883; note; note; Gupta, M., Mazumder, U.K., Kumar, R.S., Kumar, T.S., (2004) Acta Pharmacol. Sin., 25, p. 1070; Bhattacharyya, A., Choudhuri, T., Pal, S., Chattopadhyay, S., Datta, G.K., Sa, G., Das, T., (2003) Carcinogensis, 24, p. 75; note; note; Lowry, O.H., Roesebrough, N.J., Farr, A.L., Randall, R.J., (1951) J. Biol. Chem., 193, p. 265; Moron, M.S., Depierre, J.W., Mannervik, B., (1979) Biochim. Biophys. Acta, 5820, p. 62; note; Yagi, K., (1991) Chem. Phys. Lipids, 45, p. 337; Sinclair, A.J., Barnett, A.H., Lunie, J., (1990) Br. J. Hosp. Med., 43, p. 334",
year = "2006",
doi = "10.1016/j.bmcl.2005.11.044",
language = "English",
volume = "16",
pages = "1366--1370",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "5",

}

Design, synthesis, and evaluation of novel 6-chloro-/fluorochromone derivatives as potential topoisomerase inhibitor anticancer agents. / Ishar, M.P.S.; Singh, G.; Singh, S.; Sreenivasan, K.K.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 16, No. 5, 2006, p. 1366-1370.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Design, synthesis, and evaluation of novel 6-chloro-/fluorochromone derivatives as potential topoisomerase inhibitor anticancer agents

AU - Ishar, M.P.S.

AU - Singh, G.

AU - Singh, S.

AU - Sreenivasan, K.K.

N1 - Cited By :74 Export Date: 10 November 2017 CODEN: BMCLE Correspondence Address: Ishar, M.P.S.; Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143 005, Punjab, India; email: mpsishar@yahoo.com Chemicals/CAS: Antineoplastic Agents; Chromones; DNA Topoisomerases, EC 5.99.1.-; Enzyme Inhibitors References: Champaux, J., (1990) DNA Topology and Its Biological Effects, p. 217. , J.C. Wang N.R. Cozarelli Cold Spring Harbor Laboratory Cold Spring Harbor, NY; Hsieh, T.-S., (1990) DNA Topology and Its Biological Effects, p. 243. , J.C. Wang N.R. Cozarelli Cold Spring Harbor Laboratory Cold Spring Harbor, NY; Caserta, M., Amadei, A., Camilloni, G., Di Mauro, E., (1990) Biochemistry, 29, p. 8152; Harrnon, F.G., Digate, R.J., Kowalczykowski, S.C., (1999) Mol. Cell, 3, p. 611; Nagarajan, M., Morrell, A., Fort, B.C., Meckley, M.R., Antony, S., Kholhagen, G., Pommier, Y., Cushman, M., (2004) J. Med. Chem., 47, p. 5651; Pommier, Y., Tanizawa, A., (1993) Cancer Chemotherapy, p. 214. , J. Hickman T. Tritton Blackwell Scientific Publications Oxford; Chen, A.U., Liu, L.F., (1994) Annu. Rev. Pharmacol. Toxicol., 94, p. 194; Zewail-Foote, M., Hurley, L., (1999) Anti-Cancer Drug Des., 14, p. 1; Levine, C., Hiasa, H., Marians, K.J., (1998) Biochim. Biophys. Acta, 1400, p. 29; Potmesil, M., Kohn, K.K., (1991) Topoisomerases in Cancer, , Oxford University Press: New York, Chapter 2; Osheroff, N., (1989) Pharmacol. Ther., 41, p. 223; Spicer, J., Finlay, G., Baguley, B., Velea, L., Graves, D., Denny, W., (1999) Anti-Cancer Drug Des., 14, p. 37; Gootz, T.D., Birghty, K.E., (1998) The Quinolones, p. 29. , V.T. Andriole 2nd ed. Academic Press San Diego; Hooper, D.C., (2001) Clin. Infect. Dis., 32, p. 9; Fan, J.-Y., Sun, D., Yu, H., Kerwin, S.M., Hurley, L.H., (1995) J. Med. Chem., 38, p. 408; Laco, G.S., Du, W., Kohlhagen, G., Sayer, J.M., Jerina, D.M., Burke, T.G., Curran, D.P., Pommier, Y., (2004) Biorg. Med. Chem., 12, p. 5225; Cianchetta, G., Mannhold, R., Cruciani, G., Baroni, M., Cecchetti, V., (2004) J. Med. Chem., 47, p. 3193; Hsiang, Y.-H., Hertzberg, R., Hecht, S., Liu, L.F., (1985) J. Biol. Chem., 260, p. 14873; Mhaske, S.B., Argade, N.P., (2004) J. Org. Chem., 69, p. 4563; Nagarajan, M., Xiao, X., Antony, S., Kohlhagen, G., Pommier, Y., Cushman, M., (2003) J. Med. Chem., 46, p. 5712; Wall, M.E., (1998) Med. Res. Rev., 18, p. 299; Cragg, G.M., Newman, D.J., (2004) J. Nat. Prod., 67, p. 232; Osheroff, N., Zechiedrich, E.L., Gale, K.C., (1991) BioEssays, 13, p. 269; Rahier, N.J., Eisenhauer, B.M., Gao, R., Jones, S.H., Shannon, R.G., Hecht, S.M., (2004) Org. Lett., 6, p. 321; Arimondo, P., Boukarim, C., Bailly, C., Dauzonne, D., Monneret, C., (2000) Anti-Cancer Drug Des., 15, p. 413; Xiao, Z., Vance, J.R., Bastow, K.F., Brossi, A., Wang, H.-K., Lee, K.-H., (2004) Bioorg. Med. Chem. Lett., 12, p. 3363; Cassady, J.M., Baird, W.M., Chang, C.J., (1990) J. Nat. Prod., 53, p. 23; Kupchan, S.M., Streelman, D.R., Sneden, A.T., (1980) J. Nat. Prod., 43, p. 296; Kim, M.Y., Na, Y., Vankayalapati, H., Gleason-Guzman, M., (2003) J. Med. Chem., 46, p. 2958; Kwok, Y., Sun, D., Clement, J., Hurley, L., (1999) Anti-Cancer Drug Des., 14, p. 443; Domagala, J.M., (1994) J. Antimicrob. Chemother., 33, p. 685; Bryskier, A., Chantot, J.-F., (1995) Drugs, 49 (SUPPL. 2), p. 16; Gootz, T.D., Brighty, K.E., (1996) Med. Res. Rev., 16, p. 433; Xia, Y., Yang, Z.-Y., Xia, P., Hackl, T., Hamel, E., Mauger, A., Wu, J.-H., Lee, K.-H., (2001) J. Med. Chem., 44, p. 3932; Ishar, M.P.S., Kumar, K., Singh, R., (1998) Tetrahedron Lett., 39, p. 6547; Singh, G., Singh, R., Girdhar, N.K., Ishar, M.P.S., (2002) Tetraherdon, 58, p. 2471; Singh, G., Singh, L., Ishar, M.P.S., (2002) Tetraherdon, 58, p. 7883; note; note; Gupta, M., Mazumder, U.K., Kumar, R.S., Kumar, T.S., (2004) Acta Pharmacol. Sin., 25, p. 1070; Bhattacharyya, A., Choudhuri, T., Pal, S., Chattopadhyay, S., Datta, G.K., Sa, G., Das, T., (2003) Carcinogensis, 24, p. 75; note; note; Lowry, O.H., Roesebrough, N.J., Farr, A.L., Randall, R.J., (1951) J. Biol. Chem., 193, p. 265; Moron, M.S., Depierre, J.W., Mannervik, B., (1979) Biochim. Biophys. Acta, 5820, p. 62; note; Yagi, K., (1991) Chem. Phys. Lipids, 45, p. 337; Sinclair, A.J., Barnett, A.H., Lunie, J., (1990) Br. J. Hosp. Med., 43, p. 334

PY - 2006

Y1 - 2006

N2 - 6-Chloro-2-pyrrolidino-/morpholino-/piperidino-/N-methylpiperazino-3- formyl-chromones (13-16) and 6-fluoro-2,7-di-morpholino-/piperidino-/N- methylpiperazino-3-formylchromones (17-19) have been synthesized as potential topoisomerase inhibitor anticancer agents, and evaluated, in vitro, against Ehrlich ascites carcinoma (EAC) cells, and also in vivo on EAC bearing mice. The compounds displayed promising anticancer activity under these test systems and shall serve as useful 'leads' for further design. © 2005 Elsevier Ltd. All rights reserved.

AB - 6-Chloro-2-pyrrolidino-/morpholino-/piperidino-/N-methylpiperazino-3- formyl-chromones (13-16) and 6-fluoro-2,7-di-morpholino-/piperidino-/N- methylpiperazino-3-formylchromones (17-19) have been synthesized as potential topoisomerase inhibitor anticancer agents, and evaluated, in vitro, against Ehrlich ascites carcinoma (EAC) cells, and also in vivo on EAC bearing mice. The compounds displayed promising anticancer activity under these test systems and shall serve as useful 'leads' for further design. © 2005 Elsevier Ltd. All rights reserved.

U2 - 10.1016/j.bmcl.2005.11.044

DO - 10.1016/j.bmcl.2005.11.044

M3 - Article

VL - 16

SP - 1366

EP - 1370

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 5

ER -