The β-diketone scaffold, found in natural products like curcuminoids, exhibits exceptional antibacterial, neuroprotective, and anticancer properties in both natural and synthetic analogs. Moreover, β-diketones are known to form complexes with almost every metal, and they have been used as supporting ligands for Ti(IV), Ru(II), Pd(II) and Pt-based anticancer agents. Therefore, drawing inspiration from nature, medicinal inorganic chemistry allows the development of more potent, clinically effective, and less toxic metal-based antiproliferative drugs with improved selectivity towards tumor cells. The substituents on the β-diketonate moiety play a crucial role in modulating the toxic side effects of the resulting complexes. Fluorine-containing compounds are relevant in modern medicinal chemistry, and substituting methyl groups with trifluoromethyl ones in a molecule might be expected to induce great changes in molecular and biological properties. Apart from metal-curcumin complexes, very few studies on the anticancer activity of homoleptic first-row transition metal complexes with β-diketonate ligands have been described in the literature to date. We report here a study on the synthesis, characterization, and biological evaluation of new homoleptic first-row transition metal(II) complexes. In particular, we report the synthesis of Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes of the β-diketonate ligands derived from 1,3-bis(3,5-bis(trifluoromethyl)phenyl)-3-hydroxyprop-2-en-1-one (HLCF3), 1,3-dimesitylpropane-1,3-dione (HLMes) and 1,3-diphenylpropane-1,3-dione (HLPh). We carried out a screening of the newly synthesized metal(II) compounds against a panel of human cancer cell lines derived from different solid tumors, to investigate the structure-activity relationships. Except for iron derivatives, most showed significant antitumor properties, even against cisplatin-resistant cells.
Exploring fluorinated and non-fluorinated β-diketonates: synthesis and biological evaluation of first-row transition metal(II) complexes for cancer treatment
Jo' Del GobboPrimo
;Maura PelleiSecondo
;Carlo Santini;Miriam Caviglia;
2024-01-01
Abstract
The β-diketone scaffold, found in natural products like curcuminoids, exhibits exceptional antibacterial, neuroprotective, and anticancer properties in both natural and synthetic analogs. Moreover, β-diketones are known to form complexes with almost every metal, and they have been used as supporting ligands for Ti(IV), Ru(II), Pd(II) and Pt-based anticancer agents. Therefore, drawing inspiration from nature, medicinal inorganic chemistry allows the development of more potent, clinically effective, and less toxic metal-based antiproliferative drugs with improved selectivity towards tumor cells. The substituents on the β-diketonate moiety play a crucial role in modulating the toxic side effects of the resulting complexes. Fluorine-containing compounds are relevant in modern medicinal chemistry, and substituting methyl groups with trifluoromethyl ones in a molecule might be expected to induce great changes in molecular and biological properties. Apart from metal-curcumin complexes, very few studies on the anticancer activity of homoleptic first-row transition metal complexes with β-diketonate ligands have been described in the literature to date. We report here a study on the synthesis, characterization, and biological evaluation of new homoleptic first-row transition metal(II) complexes. In particular, we report the synthesis of Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes of the β-diketonate ligands derived from 1,3-bis(3,5-bis(trifluoromethyl)phenyl)-3-hydroxyprop-2-en-1-one (HLCF3), 1,3-dimesitylpropane-1,3-dione (HLMes) and 1,3-diphenylpropane-1,3-dione (HLPh). We carried out a screening of the newly synthesized metal(II) compounds against a panel of human cancer cell lines derived from different solid tumors, to investigate the structure-activity relationships. Except for iron derivatives, most showed significant antitumor properties, even against cisplatin-resistant cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
