2-(3-Aryl-2-propenoyl)-3-methylquinoxaline-1,4-dioxides: A novel cluster of tumor-specific cytotoxins which reverse multidrug resistance

Umashankar Das, Hari N. Pati, Atulya K. Panda, Erik De Clercq, Jan Balzarini, J. Molnár, Zoltán Baráth, I. Ocsovszki, Masami Kawase, Li Zhou, Hiroshi Sakagami, Jonathan R. Dimmock

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

A series of 2-(3-aryl-2-propenoyl)-3-methylquinoxaline-1,4-dioxides 3a-l were prepared by condensation of various aryl aldehydes with 2-acetyl-3-methylquinoxaline-1,4-dioxide 2. These compounds inhibit the growth of human Molt 4/C8 and CEM T-lymphocytes and the IC50 values are mainly in the 5-30 μM range. The quinoxaline 1,4-dioxide 3j inhibited the growth of 58 human tumor cell lines, particularly leukemic and breast cancer neoplasms. All of the compounds 3a-l reversed the multidrug resistance (MDR) properties of murine L-5178Y leukemic cells which were transfected with the human MDR1 gene. The MDR-reversing effect may be due to the conjugated π-electron system forming a weak electron charge transfer complex with the P-glycoprotein-mediated efflux pump. The compounds in series 2 and 3 were assessed against HL-60, HSC-2, HSC-3 and HSC-4 malignant cells as well as HGF, HPC and HPLF normal cell lines which revealed that the majority of the compounds displayed a greater toxicity to neoplastic than normal cells. Various ways in which the project may be expanded are presented.

Original languageEnglish
Pages (from-to)3909-3915
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number11
DOIs
Publication statusPublished - Jun 1 2009

Fingerprint

Cytotoxins
Multiple Drug Resistance
Tumors
Cells
T-cells
Electrons
P-Glycoprotein
Aldehydes
Breast Neoplasms
Toxicity
Charge transfer
Condensation
Neoplasms
Genes
Pumps
Growth
Tumor Cell Line
Inhibitory Concentration 50
T-Lymphocytes
Cell Line

Keywords

  • α,β-Unsaturated ketones
  • Cytotoxicity
  • Multidrug resistance revertants
  • QSAR
  • Quinoxalines
  • Structure-activity relationships

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

2-(3-Aryl-2-propenoyl)-3-methylquinoxaline-1,4-dioxides : A novel cluster of tumor-specific cytotoxins which reverse multidrug resistance. / Das, Umashankar; Pati, Hari N.; Panda, Atulya K.; Clercq, Erik De; Balzarini, Jan; Molnár, J.; Baráth, Zoltán; Ocsovszki, I.; Kawase, Masami; Zhou, Li; Sakagami, Hiroshi; Dimmock, Jonathan R.

In: Bioorganic and Medicinal Chemistry, Vol. 17, No. 11, 01.06.2009, p. 3909-3915.

Research output: Contribution to journalArticle

Das, Umashankar ; Pati, Hari N. ; Panda, Atulya K. ; Clercq, Erik De ; Balzarini, Jan ; Molnár, J. ; Baráth, Zoltán ; Ocsovszki, I. ; Kawase, Masami ; Zhou, Li ; Sakagami, Hiroshi ; Dimmock, Jonathan R. / 2-(3-Aryl-2-propenoyl)-3-methylquinoxaline-1,4-dioxides : A novel cluster of tumor-specific cytotoxins which reverse multidrug resistance. In: Bioorganic and Medicinal Chemistry. 2009 ; Vol. 17, No. 11. pp. 3909-3915.
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