Stepwise assembly of platinum–folic acid conjugates

Folates and folate-like molecules represent a class of vectors for drug targeting and delivery. The folate receptor (FR) is overexpressed in many human cancers, therefore folate-cytotoxic drug conjugates can deliver therapeutic agents specifically to FR positive tumours. We have linked, directly through one of the carboxylate functionalities of the folic acid (α or γ), two different chelating arms for a cytotoxic platinum moiety, namely a diamine and a dicarboxylate. Five different derivatives were synthesised by multi-step procedures, purified and characterised; unfortunately, they resulted barely soluble in water, thereby precluding any biochemical and biological tests.

Graphical abstractFolates can act as vectors for drugs, since the folate receptor is overexpressed in many human cancers and can recognise and internalise folate-drug conjugates in tumour cells. We linked to folic acid two different chelating arms for a cytotoxic platinum moiety and synthesised five different derivatives by multi-step procedures.Figure optionsDownload full-size imageDownload as PowerPoint slide