Design, synthesis and cytotoxicity studies of dithiocarbamate ester derivatives of emetine in prostate cancer cell lines

Emmanuel S. Akinboye, Zebalda D. Bamji, Bernard Kwabi-Addo, David Ejeh, Robert L. Copeland, Samuel R. Denmeade, Oladapo Bakare

Research output: Contribution to journalArticlepeer-review

Abstract

A small library of emetine dithiocarbamate ester derivatives were synthesized in 25-86% yield via derivatization of the N2′- position of emetine. Anticancer evaluation of these compounds in androgen receptor positive LNCaP and androgen receptor negative PC3 and DU145 prostate cancer cell lines revealed time dependent and dose-dependent cytotoxicity. With the exception of compound 4c, all the dithiocarbamate ester analogs in this study showed appreciable potency in all the prostate cancer cell lines (regardless of whether it is androgen receptor positive or negative) with a cytotoxicity IC50 value ranging from 1.312 ± 0.032 μM to 5.201 ± 0.125 μM by day 7 of treatment. Compared to the sodium dithiocarbamate salt 1, all the dithiocarbamate ester analogs (2 and 4a-4g) displayed lower cytotoxicity than compound 1 (PC3, IC50 = 0.087 ± 0.005 μM; DU145, IC50 = 0.079 ± 0.003 μM and LNCaP, IC50 = 0.079 ± 0.003 μM) on day 7 of treatment. Consequently, it appears that S-alkylation of compound 1 leads to a more stable dithiocarbamate ester derivative that resulted in lower anticancer activity in the prostate cancer cell lines.

Original languageEnglish (US)
Pages (from-to)5839-5845
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume23
Issue number17
DOIs
StatePublished - Sep 1 2015

Keywords

  • Anti-cancer activities
  • Dithiocarbamate ester
  • Emetine
  • Emetine derivatives
  • Prostate cancer

ASJC Scopus subject areas

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

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