Cytotoxic properties of the alkaloid rutaecarpine and its oligocyclic derivatives and chemical modifications to enhance water-solubility

Bioorg Med Chem Lett. 2017 Nov 1;27(21):4937-4941. doi: 10.1016/j.bmcl.2017.08.045.

Guozheng Huang ¹, Antonios Drakopoulos ², Marco Saedtler ², Huijuan Zou ³, Lorenz Meinel ², Jörg Heilmann ⁴, Michael Decker ⁵

Affiliations

1 Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany; College of Life and Environmental Sciences, Shanghai Normal University, Shanghai 201418, PR China.
2 Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
3 College of Life and Environmental Sciences, Shanghai Normal University, Shanghai 201418, PR China.
4 Institute of Pharmacy, University of Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany.
5 Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany. Electronic address: michael.decker@uni-wuerzburg.de.

PMID: 28958621 DOI: 10.1016/j.bmcl.2017.08.045

Abstract

The alkaloid rutaecarpine and its derivatives have been described as cytotoxic and hold potential as antitumor agents. Nevertheless, their synthesis is demanding and compounds display poor water solubility. Herein, we describe the synthesis of two sets of rutaecarpine derivatives with amine functions to improve solubility. Using a classic shake-flask experiment and a potentiometric titration platform, the water solubility of the compounds was determined. Solubility improved significantly with the amine functions connected over the indole-N atom. Reduction of metabolic activity and cell viability on HeLa cells was in the same range or better for these derivatives compared to the chemically unaltered parent compounds prepared in a new synthetic procedure established in our group.

Keywords

Cytotoxicity; Rutaecarpine; SiriusT3; Solubility.

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