1. New hybrids derived from podophyllic aldehyde and diterpenylhydroquinones with selectivity toward osteosarcoma cells
- Author
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Martin Perez-Andres, Ángela P Hernández, Manuel Fuentes, Paula Díez, Arturo San Feliciano, David Díez, Pablo A. García, José M. Miguel del Corral, Ma Angeles Castro, Ministerio de Economía y Competitividad (España), Junta de Castilla y León, Instituto de Salud Carlos III, and European Commission
- Subjects
0301 basic medicine ,Stereochemistry ,Cyclolignans ,Cytotoxicity ,Apoptosis ,Hybrids ,Cell cycle ,01 natural sciences ,Biochemistry ,Aldehyde ,03 medical and health sciences ,Drug Discovery ,Podophyllic aldehyde ,chemistry.chemical_classification ,Osteosarcoma ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Biological activity ,0104 chemical sciences ,Quinone ,030104 developmental biology ,Cell culture ,Diterpenylnaphthohydroquinones ,Linker - Abstract
A new family of molecular hybrids, between cyclolignans related to podophyllic aldehyde and several diterpenylnaphthohydroquinones (DNHQ), was prepared and its biological activity evaluated in several human solid tumor cell lines, which are representative of the most prevalent solid tumors in the Western world. Both cyclolignan and quinone fragments were linked through aliphatic or aromatic spacers. The new hybrid family was evaluated for its cytotoxicity, and it was found that the hybrids were several times more potent against the osteosarcoma cell line MG-63 than against MCF-7 and HT-29 cell lines. The presence of an aromatic ring in the linker gave the most potent and selective agent, improving the cytotoxicity of the parent compounds. Cell cycle studies demonstrated that this hybrid induces a strong and rapid apoptotic effect and arrests cells at the G2/M phase of the cell cycle, in the same way that the parent compound podophyllic aldehyde does., Financial support came from Spanish MINECO (CTQ2015-68175-R, AGL2016-79813-C2-2-R), Junta de Castilla y Leon (BIO/SA07/15), and ISCIII-RICET Network (RD06/0022/1004) cofinanced by the Fondo Social Europeo of the European Union (Fondos FEDER − EU. Fundacion Solorzano (FS/23-2015) has also sponsored this work. The Proteomics Unit belongs to ProteoRed, PRB2-ISCIII, supported by Grant No. PT13/0001, of the PE I+D+I 2013-2016, funded by ISCIII and FEDER. Á.P.H. and P.D. are supported by JCYL-EDU/ 346/2013 Ph.D. scholarships.
- Published
- 2018