Synthesis of novel 24-amino-25,26,27-trinorlanost-8-enes: cytotoxic and apoptotic potential in U937 cells

Roisin O'Keeffe; Olivia Kenny; Nigel P Brunton; Mohammad B Hossain; Dilip K Rai; Peter W Jones; Nora O'Brien; Anita R Maguire; Stuart G Collins

doi:10.1016/j.bmc.2015.02.034

Synthesis of novel 24-amino-25,26,27-trinorlanost-8-enes: cytotoxic and apoptotic potential in U937 cells

Bioorg Med Chem. 2015 May 1;23(9):2270-80. doi: 10.1016/j.bmc.2015.02.034. Epub 2015 Mar 5.

Authors

Roisin O'Keeffe¹, Olivia Kenny², Nigel P Brunton³, Mohammad B Hossain⁴, Dilip K Rai⁴, Peter W Jones⁵, Nora O'Brien⁶, Anita R Maguire⁷, Stuart G Collins⁸

Affiliations

¹ Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Ireland.
² School of Food and Nutritional Sciences, University College Cork, Ireland.
³ School of Agriculture and Food Science, University College Dublin, Dublin 4, Ireland.
⁴ Food Biosciences Department, Teagasc Food Research Centre, Ashtown, Dublin 15, Ireland.
⁵ Department of Zoology, Ecology and Plant Science, University College Cork, Ireland.
⁶ School of Food and Nutritional Sciences, University College Cork, Ireland. Electronic address: nob@ucc.ie.
⁷ Department of Chemistry and School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Ireland. Electronic address: a.maguire@ucc.ie.
⁸ Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Ireland. Electronic address: stuart.collins@ucc.ie.

PMID: 25800433
DOI: 10.1016/j.bmc.2015.02.034

Abstract

In the present study, the synthesis of a range of novel 24-amino-25,26,27-trinorlanost-8-ene derivatives including 24-piperadino-trinorlanost-8-enes, 24-piperazino-trinorlanost-8-enes, 24-morpholino-trinorlanost-8-enes, and 24-diethylamino-trinorlanost-8-enes is reported and their cytotoxic and apoptotic potential evaluated in U937 cell lines. Excellent IC₅₀ results for piperidine and 1-(2-hydroxyethyl)piperazine derivatives have been observed (IC₅₀ values of 1.9 μM and 2.7 μM in U937 cells, respectively).

Keywords: Apoptosis; Lanostanes; Oxidative cleavage; Reductive amination; U937 cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects*
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Humans
Lanosterol* / analogs & derivatives
Lanosterol* / chemical synthesis
Lanosterol* / chemistry
Lanosterol* / pharmacology
Molecular Conformation
Structure-Activity Relationship
U937 Cells

Substances

Lanosterol