Novel metal complexes of naphthalimide–cyclam conjugates as potential multi-target receptor tyrosine kinase (RTK) inhibitors: Synthesis and biological evaluation

•Novel metal complexes of naphthalimide–cyclam conjugates were designed, synthesized.•All of the compounds were evaluated of their antitumor activities.•Zn(II) and Cr(III) complexes displayed as multi-target RTK inhibitors.•Representative compound 8a showed antiproliferative and antiangiogenic activities.

A novel series of metal complexes of naphthalimide–cyclam conjugates were synthesized and their in vitro antitumor activities were evaluated. The newly-synthesized compounds showed huge diversity of antiproliferative potency due to variety of metal ions and length of alkyl chains, among which the Zn(II) and Cr(III) complexes exhibited comparable antiproliferative activities with amonafide via multiple tyrosine kinase inhibition. Further research revealed that the representative compound 8a displayed broad-spectrum antiproliferative activity against 15 cancer cell lines with average IC50 value 10.18 ± 3.25 μM, and effective antiangiogenic activity on human microvascular endothelial cells (HMEC-1). In brief, metal complexes of naphthalimide–cyclam conjugates were firstly designed and synthesized as multi-target tyrosine kinase inhibitors and proved of their antitumor capacities.

Graphical abstractA novel series of metal complexes of naphthalimide–cyclam conjugates were designed and synthesized, which displayed as multi-target RTK inhibitors. Representative compound 8a exhibited both broad-spectrum antiproliferative capacity and antiangiogenic activity.Figure optionsDownload full-size imageDownload as PowerPoint slide