Synthesis of jacaranone-derived nitrogenous cyclohexadienones and their antiproliferative and antiprotozoal activities

Armin Presser, Gunda Lainer, Nadine Kretschmer, Wolfgang Schuehly, Robert Saf, Marcel Kaiser, Marc Manuel Kalt

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The cytotoxic and antiprotozoal activities of the phytoquinoide, jacaranone, and related compounds have been an ongoing topic in recent drug discovery. Starting from the natural product-derived cyclohexadienone scaffold, a series of nitrogen-containing derivatives were synthesized and subsequently evaluated for their antiproliferative and antiprotozoal activity. Anticancer potency was analyzed using different types of cancer cell lines: MDA-MB-231 breast cancer, CCRF-CEM leukemia, HCT-116 colon cancer, U251 glioblastoma, and, in addition, non-tumorigenic MRC-5 lung fibroblasts. Antiproliferative activities at micromolar concentrations could be shown. Antiprotozoal activity was assessed against Plasmodium falciparum NF54 and Trypanosoma brucei rhodesiense STIB900. For all compounds, selectivity indices (SI) were calculated based on assessed cytotoxicity towards L6 cells. In addition, the structure-activity-relationships and physicochemical parameters of these compounds are discussed.

Original languageEnglish
Article number2902
JournalMolecules
Volume23
Issue number11
DOIs
Publication statusPublished - 7 Nov 2018

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Keywords

  • Antiproliferative activity
  • Antiprotozoal activity
  • Green chemistry
  • Jacaranone
  • Natural products

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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