Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones

Jonathan R. Dimmock; Maniyan P. Padmanilayam; Gordon A. Zello; Kurt H. Nienaber; Theresa M. Allen; Cheryl L. Santos; Erik De Clercq; Jan Balzarini; Elias K. Manavathu; James P. Stables

doi:10.1016/S0223-5234(02)01444-7

Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones

Jonathan R. Dimmock, Maniyan P. Padmanilayam, Gordon A. Zello, Kurt H. Nienaber, Theresa M. Allen, Cheryl L. Santos, Erik De Clercq, Jan Balzarini, Elias K. Manavathu, James P. Stables

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

98 Scopus citations

Abstract

A series of 2,6-bis(arylidene)cycloalkanones (1) and related compounds containing one or two substituents at the four position of the cyclohexyl ring were prepared and shown to display cytotoxic activity towards murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In some of the series of compounds, positive correlations were noted between the potencies of the enones and the magnitude of the Hammett σ values of the aryl substituents. Four representative compounds were cytotoxic to a number of human tumours in vitro, particularly towards colon cancer and leukemic cells. A noteworthy feature of the compounds prepared in this study is that, in general, they were well tolerated when administered to rodents. A number of lead molecules emerged from this investigation as well as guidelines for future expansion of these series of compounds.

Original language	English (US)
Pages (from-to)	169-177
Number of pages	9
Journal	European Journal of Medicinal Chemistry
Volume	38
Issue number	2
DOIs	https://doi.org/10.1016/S0223-5234(02)01444-7
State	Published - Feb 1 2003
Externally published	Yes

Keywords

Bioscreens
Cytotoxicity
Structure-activity relationships
α,β-Unsaturated ketones

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)01444-7

Cite this

@article{29b606671722427f8b3f968611b1422d,

title = "Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones",

abstract = "A series of 2,6-bis(arylidene)cycloalkanones (1) and related compounds containing one or two substituents at the four position of the cyclohexyl ring were prepared and shown to display cytotoxic activity towards murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In some of the series of compounds, positive correlations were noted between the potencies of the enones and the magnitude of the Hammett σ values of the aryl substituents. Four representative compounds were cytotoxic to a number of human tumours in vitro, particularly towards colon cancer and leukemic cells. A noteworthy feature of the compounds prepared in this study is that, in general, they were well tolerated when administered to rodents. A number of lead molecules emerged from this investigation as well as guidelines for future expansion of these series of compounds.",

keywords = "Bioscreens, Cytotoxicity, Structure-activity relationships, α,β-Unsaturated ketones",

author = "Dimmock, {Jonathan R.} and Padmanilayam, {Maniyan P.} and Zello, {Gordon A.} and Nienaber, {Kurt H.} and Allen, {Theresa M.} and Santos, {Cheryl L.} and {De Clercq}, Erik and Jan Balzarini and Manavathu, {Elias K.} and Stables, {James P.}",

note = "Funding Information: The following organizations are thanked for their financial support of this study, namely Purdue Neuroscience Company, USA (J. R. D.), National Cancer Institute of Canada (T. M. A.), Flemish Fonds Voor Geneeskundig Weterschappelijk Onderzoek (E. D. C., J. B.) and the National Institute for Neurological Disorders and Stroke (J. P. S.). The National Cancer Institute, USA, is thanked for the evaluations using a panel of human tumour cell lines. ",

year = "2003",

month = feb,

day = "1",

doi = "10.1016/S0223-5234(02)01444-7",

language = "English (US)",

volume = "38",

pages = "169--177",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson SAS",

number = "2",

}

TY - JOUR

T1 - Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones

AU - Dimmock, Jonathan R.

AU - Padmanilayam, Maniyan P.

AU - Zello, Gordon A.

AU - Nienaber, Kurt H.

AU - Allen, Theresa M.

AU - Santos, Cheryl L.

AU - De Clercq, Erik

AU - Balzarini, Jan

AU - Manavathu, Elias K.

AU - Stables, James P.

N1 - Funding Information: The following organizations are thanked for their financial support of this study, namely Purdue Neuroscience Company, USA (J. R. D.), National Cancer Institute of Canada (T. M. A.), Flemish Fonds Voor Geneeskundig Weterschappelijk Onderzoek (E. D. C., J. B.) and the National Institute for Neurological Disorders and Stroke (J. P. S.). The National Cancer Institute, USA, is thanked for the evaluations using a panel of human tumour cell lines.

PY - 2003/2/1

Y1 - 2003/2/1

N2 - A series of 2,6-bis(arylidene)cycloalkanones (1) and related compounds containing one or two substituents at the four position of the cyclohexyl ring were prepared and shown to display cytotoxic activity towards murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In some of the series of compounds, positive correlations were noted between the potencies of the enones and the magnitude of the Hammett σ values of the aryl substituents. Four representative compounds were cytotoxic to a number of human tumours in vitro, particularly towards colon cancer and leukemic cells. A noteworthy feature of the compounds prepared in this study is that, in general, they were well tolerated when administered to rodents. A number of lead molecules emerged from this investigation as well as guidelines for future expansion of these series of compounds.

AB - A series of 2,6-bis(arylidene)cycloalkanones (1) and related compounds containing one or two substituents at the four position of the cyclohexyl ring were prepared and shown to display cytotoxic activity towards murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In some of the series of compounds, positive correlations were noted between the potencies of the enones and the magnitude of the Hammett σ values of the aryl substituents. Four representative compounds were cytotoxic to a number of human tumours in vitro, particularly towards colon cancer and leukemic cells. A noteworthy feature of the compounds prepared in this study is that, in general, they were well tolerated when administered to rodents. A number of lead molecules emerged from this investigation as well as guidelines for future expansion of these series of compounds.

KW - Bioscreens

KW - Cytotoxicity

KW - Structure-activity relationships

KW - α,β-Unsaturated ketones

UR - http://www.scopus.com/inward/record.url?scp=0037293779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037293779&partnerID=8YFLogxK

U2 - 10.1016/S0223-5234(02)01444-7

DO - 10.1016/S0223-5234(02)01444-7

M3 - Article

C2 - 12620661

AN - SCOPUS:0037293779

SN - 0223-5234

VL - 38

SP - 169

EP - 177

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

IS - 2

ER -

Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this