Cytotoxic 1,3-diarylidene-2-tetralones and related compounds

Jonathan R. Dimmock; Maniyan P. Padmanilyam; Gordon A. Zello; J. Wilson Quail; Eliud O. Oloo; Jared S. Prisciak; Heinz Bernhard Kraatz; Arten Cherkasov; Jeremy S. Lee; Theresa M. Allen; Cheryl L. Santos; Elias K. Manavathu; Erik De Clercq; Jan Balzarini; James P. Stables

doi:10.1016/S0223-5234(02)01402-2

Cytotoxic 1,3-diarylidene-2-tetralones and related compounds

Jonathan R. Dimmock, Maniyan P. Padmanilyam, Gordon A. Zello, J. Wilson Quail, Eliud O. Oloo, Jared S. Prisciak, Heinz Bernhard Kraatz, Arten Cherkasov, Jeremy S. Lee, Theresa M. Allen, Cheryl L. Santos, Elias K. Manavathu, Erik De Clercq, Jan Balzarini, James P. Stables

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

A number of 1,3-arylidene-2-tetralones 1, 2 and 4 were synthesised and demonstrated cytotoxic activity towards murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In general, the related 1-arylidene-2-tetralones 3 possessed lower potencies in these screens than the compounds in series 1 and 4. Approximately, half of the compounds were evaluated against a panel of human tumour cell lines. In this screen, most of the enones were more cytotoxic than the established anticancer agent melphalan and some demonstrated selective toxicity towards leukemic and colon cancer cells. The modes of action of representative compounds include interfering with the biosyntheses of nucleic acids and proteins as well as altering redox potentials. The compounds were well tolerated when administered intraperiteonally to mice. Thus these novel enones are promising prototypic molecules due to their potent cytotoxic properties and lack of significant murine toxicity.

Original language	English (US)
Pages (from-to)	813-824
Number of pages	12
Journal	European Journal of Medicinal Chemistry
Volume	37
Issue number	10
DOIs	https://doi.org/10.1016/S0223-5234(02)01402-2
State	Published - Oct 2002
Externally published	Yes

Keywords

2-Tetralones
Cytotoxicity
Murine toxicity
Redox potentials

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/S0223-5234(02)01402-2

Cite this

Dimmock, J. R., Padmanilyam, M. P., Zello, G. A., Wilson Quail, J., Oloo, E. O., Prisciak, J. S., Kraatz, H. B., Cherkasov, A., Lee, J. S., Allen, T. M., Santos, C. L., Manavathu, E. K., De Clercq, E., Balzarini, J., & Stables, J. P. (2002). Cytotoxic 1,3-diarylidene-2-tetralones and related compounds. European Journal of Medicinal Chemistry, 37(10), 813-824. https://doi.org/10.1016/S0223-5234(02)01402-2

Dimmock, JR, Padmanilyam, MP, Zello, GA, Wilson Quail, J, Oloo, EO, Prisciak, JS, Kraatz, HB, Cherkasov, A, Lee, JS, Allen, TM, Santos, CL, Manavathu, EK, De Clercq, E, Balzarini, J & Stables, JP 2002, 'Cytotoxic 1,3-diarylidene-2-tetralones and related compounds', European Journal of Medicinal Chemistry, vol. 37, no. 10, pp. 813-824. https://doi.org/10.1016/S0223-5234(02)01402-2

@article{5022d9cc830d4f8c9057f5cca1bce67d,

title = "Cytotoxic 1,3-diarylidene-2-tetralones and related compounds",

abstract = "A number of 1,3-arylidene-2-tetralones 1, 2 and 4 were synthesised and demonstrated cytotoxic activity towards murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In general, the related 1-arylidene-2-tetralones 3 possessed lower potencies in these screens than the compounds in series 1 and 4. Approximately, half of the compounds were evaluated against a panel of human tumour cell lines. In this screen, most of the enones were more cytotoxic than the established anticancer agent melphalan and some demonstrated selective toxicity towards leukemic and colon cancer cells. The modes of action of representative compounds include interfering with the biosyntheses of nucleic acids and proteins as well as altering redox potentials. The compounds were well tolerated when administered intraperiteonally to mice. Thus these novel enones are promising prototypic molecules due to their potent cytotoxic properties and lack of significant murine toxicity.",

keywords = "2-Tetralones, Cytotoxicity, Murine toxicity, Redox potentials",

author = "Dimmock, {Jonathan R.} and Padmanilyam, {Maniyan P.} and Zello, {Gordon A.} and {Wilson Quail}, J. and Oloo, {Eliud O.} and Prisciak, {Jared S.} and Kraatz, {Heinz Bernhard} and Arten Cherkasov and Lee, {Jeremy S.} and Allen, {Theresa M.} and Santos, {Cheryl L.} and Manavathu, {Elias K.} and {De Clercq}, Erik and Jan Balzarini and Stables, {James P.}",

note = "Funding Information: The authors thank the following organisations for providing financial assistance for this study, namely Purdue Neuroscience Inc., USA (J.R.D., M.P.P.), the Natural Sciences and Engineering Research Council (J.W.Q., E.O.O., H.-B.K.), the Canadian Institutes of Health Research (A.C., J.S.L.), the National Cancer Institute (T.M.A.) and the Flemish Fonds voor Geneeeskundig Wetenschappelijk Onderzoek (E.D.C., J.B.). The excellent technical assistance of L. van Berckelaer (L1210, Molt 4/C8 and CEM assays) is gratefully acknowledged, as is the US National Cancer Institute, which generated the biodata in table 7. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.",

year = "2002",

month = oct,

doi = "10.1016/S0223-5234(02)01402-2",

language = "English (US)",

volume = "37",

pages = "813--824",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson SAS",

number = "10",

}

TY - JOUR

T1 - Cytotoxic 1,3-diarylidene-2-tetralones and related compounds

AU - Dimmock, Jonathan R.

AU - Padmanilyam, Maniyan P.

AU - Zello, Gordon A.

AU - Wilson Quail, J.

AU - Oloo, Eliud O.

AU - Prisciak, Jared S.

AU - Kraatz, Heinz Bernhard

AU - Cherkasov, Arten

AU - Lee, Jeremy S.

AU - Allen, Theresa M.

AU - Santos, Cheryl L.

AU - Manavathu, Elias K.

AU - De Clercq, Erik

AU - Balzarini, Jan

AU - Stables, James P.

N1 - Funding Information: The authors thank the following organisations for providing financial assistance for this study, namely Purdue Neuroscience Inc., USA (J.R.D., M.P.P.), the Natural Sciences and Engineering Research Council (J.W.Q., E.O.O., H.-B.K.), the Canadian Institutes of Health Research (A.C., J.S.L.), the National Cancer Institute (T.M.A.) and the Flemish Fonds voor Geneeeskundig Wetenschappelijk Onderzoek (E.D.C., J.B.). The excellent technical assistance of L. van Berckelaer (L1210, Molt 4/C8 and CEM assays) is gratefully acknowledged, as is the US National Cancer Institute, which generated the biodata in table 7. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.

PY - 2002/10

Y1 - 2002/10

N2 - A number of 1,3-arylidene-2-tetralones 1, 2 and 4 were synthesised and demonstrated cytotoxic activity towards murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In general, the related 1-arylidene-2-tetralones 3 possessed lower potencies in these screens than the compounds in series 1 and 4. Approximately, half of the compounds were evaluated against a panel of human tumour cell lines. In this screen, most of the enones were more cytotoxic than the established anticancer agent melphalan and some demonstrated selective toxicity towards leukemic and colon cancer cells. The modes of action of representative compounds include interfering with the biosyntheses of nucleic acids and proteins as well as altering redox potentials. The compounds were well tolerated when administered intraperiteonally to mice. Thus these novel enones are promising prototypic molecules due to their potent cytotoxic properties and lack of significant murine toxicity.

AB - A number of 1,3-arylidene-2-tetralones 1, 2 and 4 were synthesised and demonstrated cytotoxic activity towards murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In general, the related 1-arylidene-2-tetralones 3 possessed lower potencies in these screens than the compounds in series 1 and 4. Approximately, half of the compounds were evaluated against a panel of human tumour cell lines. In this screen, most of the enones were more cytotoxic than the established anticancer agent melphalan and some demonstrated selective toxicity towards leukemic and colon cancer cells. The modes of action of representative compounds include interfering with the biosyntheses of nucleic acids and proteins as well as altering redox potentials. The compounds were well tolerated when administered intraperiteonally to mice. Thus these novel enones are promising prototypic molecules due to their potent cytotoxic properties and lack of significant murine toxicity.

KW - 2-Tetralones

KW - Cytotoxicity

KW - Murine toxicity

KW - Redox potentials

UR - http://www.scopus.com/inward/record.url?scp=0036809108&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036809108&partnerID=8YFLogxK

U2 - 10.1016/S0223-5234(02)01402-2

DO - 10.1016/S0223-5234(02)01402-2

M3 - Article

C2 - 12446039

AN - SCOPUS:0036809108

SN - 0223-5234

VL - 37

SP - 813

EP - 824

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

IS - 10

ER -

Cytotoxic 1,3-diarylidene-2-tetralones and related compounds

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this