1,2,3,4-Tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4

Lauren Lee, Ryan Davis, Jenna Vanderham, Patrice Hills, Hilary Mackay, Toni Brown, Susan L Mooberry, Moses Lee

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Eleven 1,2,3,4-tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4 (CA-4) were synthesized and their cytotoxicity against the growth of two murine cancer cell lines (B16 melanoma and L1210 leukemia) in culture was determined using an MTT assay. Two 2-thioxopyrimidine analogs 8f and 9a exhibited significant activity (IC50 < 1 μM for L1210 and <10 μM for B16 cells). Exposure of A-10 cells to 8f and 9a produced a significant reduction in cellular microtubules in interphase cells, with an EC50 value of 4.4 and 2.9 μM, respectively, for microtubule loss. Molecular modeling studies using MacSpartan indicated that the two active 2-thioxopyrimidine analogs preferably adopt a twisted conformation, similar to CA-4, affirming that conformation and structure are connected to activity.

Original languageEnglish (US)
Pages (from-to)2011-2015
Number of pages5
JournalEuropean Journal of Medicinal Chemistry
Volume43
Issue number9
DOIs
StatePublished - Sep 2008
Externally publishedYes

Fingerprint

Conformations
Microtubules
Molecular modeling
Cytotoxicity
Leukemia L1210
Assays
Experimental Melanomas
antineoplaston A10
Interphase
Cells
Inhibitory Concentration 50
Cell Line
fosbretabulin
Neoplasms

Keywords

  • Chalcone
  • Combretastatin
  • Cytotoxicity
  • Thiourea
  • Tubulin

ASJC Scopus subject areas

  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Lee, L., Davis, R., Vanderham, J., Hills, P., Mackay, H., Brown, T., ... Lee, M. (2008). 1,2,3,4-Tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4. European Journal of Medicinal Chemistry, 43(9), 2011-2015. https://doi.org/10.1016/j.ejmech.2007.11.030

1,2,3,4-Tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4. / Lee, Lauren; Davis, Ryan; Vanderham, Jenna; Hills, Patrice; Mackay, Hilary; Brown, Toni; Mooberry, Susan L; Lee, Moses.

In: European Journal of Medicinal Chemistry, Vol. 43, No. 9, 09.2008, p. 2011-2015.

Research output: Contribution to journalArticle

Lee, L, Davis, R, Vanderham, J, Hills, P, Mackay, H, Brown, T, Mooberry, SL & Lee, M 2008, '1,2,3,4-Tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4', European Journal of Medicinal Chemistry, vol. 43, no. 9, pp. 2011-2015. https://doi.org/10.1016/j.ejmech.2007.11.030
Lee, Lauren ; Davis, Ryan ; Vanderham, Jenna ; Hills, Patrice ; Mackay, Hilary ; Brown, Toni ; Mooberry, Susan L ; Lee, Moses. / 1,2,3,4-Tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4. In: European Journal of Medicinal Chemistry. 2008 ; Vol. 43, No. 9. pp. 2011-2015.
@article{74c2216288274c5c8a2ecf4a5f654377,
title = "1,2,3,4-Tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4",
abstract = "Eleven 1,2,3,4-tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4 (CA-4) were synthesized and their cytotoxicity against the growth of two murine cancer cell lines (B16 melanoma and L1210 leukemia) in culture was determined using an MTT assay. Two 2-thioxopyrimidine analogs 8f and 9a exhibited significant activity (IC50 < 1 μM for L1210 and <10 μM for B16 cells). Exposure of A-10 cells to 8f and 9a produced a significant reduction in cellular microtubules in interphase cells, with an EC50 value of 4.4 and 2.9 μM, respectively, for microtubule loss. Molecular modeling studies using MacSpartan indicated that the two active 2-thioxopyrimidine analogs preferably adopt a twisted conformation, similar to CA-4, affirming that conformation and structure are connected to activity.",
keywords = "Chalcone, Combretastatin, Cytotoxicity, Thiourea, Tubulin",
author = "Lauren Lee and Ryan Davis and Jenna Vanderham and Patrice Hills and Hilary Mackay and Toni Brown and Mooberry, {Susan L} and Moses Lee",
year = "2008",
month = "9",
doi = "10.1016/j.ejmech.2007.11.030",
language = "English (US)",
volume = "43",
pages = "2011--2015",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",
number = "9",

}

TY - JOUR

T1 - 1,2,3,4-Tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4

AU - Lee, Lauren

AU - Davis, Ryan

AU - Vanderham, Jenna

AU - Hills, Patrice

AU - Mackay, Hilary

AU - Brown, Toni

AU - Mooberry, Susan L

AU - Lee, Moses

PY - 2008/9

Y1 - 2008/9

N2 - Eleven 1,2,3,4-tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4 (CA-4) were synthesized and their cytotoxicity against the growth of two murine cancer cell lines (B16 melanoma and L1210 leukemia) in culture was determined using an MTT assay. Two 2-thioxopyrimidine analogs 8f and 9a exhibited significant activity (IC50 < 1 μM for L1210 and <10 μM for B16 cells). Exposure of A-10 cells to 8f and 9a produced a significant reduction in cellular microtubules in interphase cells, with an EC50 value of 4.4 and 2.9 μM, respectively, for microtubule loss. Molecular modeling studies using MacSpartan indicated that the two active 2-thioxopyrimidine analogs preferably adopt a twisted conformation, similar to CA-4, affirming that conformation and structure are connected to activity.

AB - Eleven 1,2,3,4-tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4 (CA-4) were synthesized and their cytotoxicity against the growth of two murine cancer cell lines (B16 melanoma and L1210 leukemia) in culture was determined using an MTT assay. Two 2-thioxopyrimidine analogs 8f and 9a exhibited significant activity (IC50 < 1 μM for L1210 and <10 μM for B16 cells). Exposure of A-10 cells to 8f and 9a produced a significant reduction in cellular microtubules in interphase cells, with an EC50 value of 4.4 and 2.9 μM, respectively, for microtubule loss. Molecular modeling studies using MacSpartan indicated that the two active 2-thioxopyrimidine analogs preferably adopt a twisted conformation, similar to CA-4, affirming that conformation and structure are connected to activity.

KW - Chalcone

KW - Combretastatin

KW - Cytotoxicity

KW - Thiourea

KW - Tubulin

UR - http://www.scopus.com/inward/record.url?scp=51149096446&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=51149096446&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2007.11.030

DO - 10.1016/j.ejmech.2007.11.030

M3 - Article

C2 - 18226429

AN - SCOPUS:51149096446

VL - 43

SP - 2011

EP - 2015

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

IS - 9

ER -