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: a_k76@txstate.edu.

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.

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