A new family of hybrids between cyclolignans related to podophyllic aldehyde, a non-lactonic cyclolignan, and purines were prepared and evaluated against several human tumour cell lines. Both fragments, cyclolignan and purine, were linked through aliphatic and aromatic chains. The influence on the cytotoxicity of the purine substitution and the nature of the linker is analyzed. The new family was slightly less cytotoxic than the parent podophyllic aldehyde, although the selectivity is maintained or even improved and among the linkers used, the presence of an aromatic ring gave the most potent and selective derivatives within the new series tested. Cell cycle and confocal studies demonstrate that these derivatives interfere with the tubulin polymerization and arrest cells at the G2/M phase, in the same way than the parent compounds podophyllotoxin and podophyllic aldehyde do.

Financial support came from Spanish Ministerio de Ciencia e Innovación (CTQ2008-02899, SAF2011-30518), Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III (RD06/0020/1037) and Junta de Castilla y León (CSI052A11-2, GR15-Experimental Therapeutics and Translational Oncology Program, SA028A10-2 and fellowship to M.V.R.) cofunded by the Fondo Europeo de Desarrollo Regional of the European Union.

Peer Reviewed