First-row transition metal complexes of naturally occurring anticancer chelators for cancer treatment

Ligands in a metal complex are crucial in determining the therapeutic effectiveness of the complex. This activity modulation is multifaceted, influenced by factors such as enhanced lipophilicity, alterations in redox and spectroscopic properties, cellular uptake, solubility, and synergistic enhancement of cytotoxicity. Complexes of first-row bioessential transition metals from vanadium (V) to copper (Cu), characterized by their variable oxidation states, intriguing redox properties, and bioessential nature, present promising avenues for developing next-generation metal complexes with organic ligands possessing intrinsic anticancer properties, particularly those derived from natural sources. This review article explores recent and up-to-date advancements in first-row transition metal complexes (V to Zn) incorporating five distinct types of naturally occurring anticancer ligands endowed with chelating properties, namely, curcumin, flavonoids, coumarin, naphthoquinone, and hypocrellins. Curcumin inherently contains an O,O-donor bidentate coordination site, while natural derivatives from the other four classes of compounds were selected for their intrinsic bidentate O,O-donor sites. These coordination sites typically consist of either two oxygen atoms from two adjacent hydroxyl (OH) groups (coumarin) or one oxygen atom from a carbonyl (C=O) group and another from a hydroxyl (OH) group (for flavonoids, naphthoquinone, and hypocrellins), ensuring sufficient thermodynamic stability of the chelate rings formed upon complexation. Emphasizing findings from our laboratory and other investigators in this burgeoning field, we explore the potential of these complexes in anticancer applications. Additionally, we explore studies involving first-row transition metal complexes coupled with naturally occurring photoactive ligands, serving as potent photosensitizers for cancer phototherapy. We conclude by addressing the prospects and challenges in this vital research area. We believe this timely compilation will benefit researchers by providing insights into recent and up-to-date findings and fostering further advancements in this emerging area.