Synthesis of Bioconjugate Sesterterpenoids with Phospholipids and Polyunsaturated Fatty Acids

Ana Gil-Mesón; Alejandro M Roncero; Ignacio E Tobal; Pilar Basabe; David Díez; Faustino Mollinedo; Isidro S Marcos

doi:10.3390/molecules21010047

Synthesis of Bioconjugate Sesterterpenoids with Phospholipids and Polyunsaturated Fatty Acids

Molecules. 2015 Dec 30;21(1):E47. doi: 10.3390/molecules21010047.

Authors

Ana Gil-Mesón¹, Alejandro M Roncero², Ignacio E Tobal³, Pilar Basabe⁴, David Díez⁵, Faustino Mollinedo^{6

7}, Isidro S Marcos⁸

Affiliations

¹ Departamento de Química Orgánica, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008 Salamanca, Spain. anagm@usal.es.
² Departamento de Química Orgánica, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008 Salamanca, Spain. alexmaron@usal.es.
³ Departamento de Química Orgánica, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008 Salamanca, Spain. ignaciotobal@usal.es.
⁴ Departamento de Química Orgánica, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008 Salamanca, Spain. pbb@usal.es.
⁵ Departamento de Química Orgánica, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008 Salamanca, Spain. ddm@usal.es.
⁶ Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer, CSIC-Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain. fmollin@usal.es.
⁷ Laboratory of Cell Death and Cancer Therapy, Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas, CSIC, C/Ramiro de Maeztu 9, 28040 Madrid, Spain. fmollin@usal.es.
⁸ Departamento de Química Orgánica, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008 Salamanca, Spain. ismarcos@usal.es.

Abstract

A series of sesterterpenoid bioconjugates with phospholipids and polyunsaturated fatty acids (PUFAs) have been synthesized for biological activity testing as antiproliferative agents in several cancer cell lines. Different substitution analogues of the original lipidic ether edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) are obtained varying the sesterterpenoid in position 1 or 2 of the glycerol or a phosphocholine or PUFA unit in position 3. Simple bioconjugates of sesterterpenoids and eicosapentaenoic acid (EPA) have been obtained too. All synthetic derivatives were tested against the human tumour cell lines HeLa (cervix) and MCF-7 (breast). Some compounds showed good IC50 (0.3 and 0.2 μM) values against these cell lines.

Keywords: PUFAs; antitumoural; bioconjugates; edelfosine; ether lipidics; sesterterpenolides.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Cell Proliferation / drug effects
Fatty Acids, Unsaturated / chemistry*
Female
HeLa Cells
Humans
MCF-7 Cells
Phospholipid Ethers
Phospholipids / chemistry*
Sesterterpenes / chemical synthesis*
Sesterterpenes / chemistry
Sesterterpenes / pharmacology

Substances

Antineoplastic Agents
Fatty Acids, Unsaturated
Phospholipid Ethers
Phospholipids
Sesterterpenes
edelfosine