title: C1,C2-ether derivatives of the Amaryllidaceae alkaloid lycorine: retention of activity of highly lipophilic analogues against cancer cells.
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.
authors.affiliation: Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Dasari
authors.affiliation: Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Laetitia Moreno Y
authors.initials: LM
authors.lastname: Banuls
authors.affiliation: Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte Sant'Angelo, Via Cintia 4, 80126 Napoli, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Masi
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Stellenbosch, Western Cape, South Africa.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pelly
authors.affiliation: Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Mathieu
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Stellenbosch, Western Cape, South Africa.
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Green
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Stellenbosch, Western Cape, South Africa.
authors.forename: Willem A L
authors.initials: WA
authors.lastname: van Otterlo
authors.affiliation: Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte Sant'Angelo, Via Cintia 4, 80126 Napoli, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Evidente
authors.affiliation: Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.affiliation: Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA. Electronic address: a_k76@txstate.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kornienko
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology; D047151:Amaryllidaceae Alkaloids / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D045744:Cell Line, Tumor; D003198:Computer Simulation; D004987:Ethers / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D019668:Liliaceae / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010617:Phenanthridines / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility
chemical_list: D000470:Alkaloids; D047151:Amaryllidaceae Alkaloids; D000970:Antineoplastic Agents; D004987:Ethers; D008055:Lipids; D010617:Phenanthridines; C015330:lycorine
keywords: Alkaloid; Apoptosis resistance; Cancer; Glioblastoma; Melanoma