C1,C2-ether derivatives of the Amaryllidaceae alkaloid lycorine: retention of activity of highly lipophilic analogues against cancer cells

  • Bioorg Med Chem Lett. 2014 Feb 1;24(3):923-7. doi: 10.1016/j.bmcl.2013.12.073.
Ramesh Dasari  1 ,  Laetitia Moreno Y Banuls  2 ,  Marco Masi  3 ,  Stephen C Pelly  4 ,  Véronique Mathieu  2 ,  Ivan R Green  4 ,  Willem A L van Otterlo  4 ,  Antonio Evidente  3 ,  Robert Kiss  2 ,  Alexander Kornienko  5
Affiliations
  • 1. Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA.
  • 2. Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium.
  • 3. Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte Sant'Angelo, Via Cintia 4, 80126 Napoli, Italy.
  • 4. Department of Chemistry and Polymer Science, Stellenbosch University, Stellenbosch, Western Cape, South Africa.
  • 5. Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA. Electronic address: [email protected].
PMID: 24393582 DOI: 10.1016/j.bmcl.2013.12.073
Abstract

As a continuation of the studies aimed at the development of new Anticancer agents derived from the Amaryllidaceae alkaloid lycorine, 35 C1,C2-ether analogues of this natural product were synthesized. The compounds were evaluated for antiproliferative activities in vitro in a panel of tumor cell lines with varied levels of Apoptosis resistance. A strong correlation between the compound lipophilicity and Anticancer activity was observed, indicating that cell permeability properties must be an important determinant in the design of lycorine-based Anticancer agents. A theoretical docking model, consistent with the experimental observations, is presented.

Keywords
Alkaloid; Apoptosis resistance; Cancer; Glioblastoma; Melanoma.