Synthesis and cytotoxicity studies of Cu(I) and Ag(I) complexes based on sterically hindered β-diketonates with different degrees of fluorination

Design, synthesis, and in vitro antitumor properties of Cu(i) and Ag(i) phosphane complexes supported by the anions of sterically hindered & beta;-diketone ligands, 1,3-dimesitylpropane-1,3-dione (HLMes) and 1,3-bis(3,5-bis(trifluoromethyl)phenyl)-3-hydroxyprop-2-en-1-one (HLCF3) featuring trifluoromethyl or methyl groups on the phenyl moieties have been reported. In order to compare the biological effects of substituents on the phenyl moieties, the analogous copper(i) and silver(i) complexes of the anion of the parent 1,3-diphenylpropane-1,3-dione (HLPh) ligand were also synthesized and included in the study. In the syntheses of the Cu(i) and Ag(i) complexes, the phosphane coligands triphenylphosphine (PPh3) and 1,3,5-triaza-7-phosphaadamantane (PTA) were used to stabilize silver and copper in the +1 oxidation state, preventing the metal ion reduction to Ag(0) or oxidation to Cu(ii), respectively. X-ray crystal structures of HLCF3 and the metal adducts [Cu(L-CF3)(PPh3)(2)] and [Ag(L-Ph)(PPh3)(2)] are also presented. The antitumor properties of both classes of metal complexes were evaluated against a series of human tumor cell lines derived from different solid tumors, by means of both 2D and 3D cell viability studies. They display noteworthy antitumor properties and are more potent than cisplatin in inhibiting cancer cell growth

Synthesis and Investigations of the Antitumor Effects of First-Row Transition Metal(II) Complexes Supported by Two Fluorinated and Non-Fluorinated β-Diketonates

The 3d transition metal (Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II)) complexes, supported by anions of sterically demanding β-diketones, 1,3-dimesitylpropane-1,3-dione (HLMes) and 1,3-bis(3,5-bis(trifluoromethyl)phenyl)-3-hydroxyprop-2-en-1-one (HLCF3), were synthesized and evaluated for their antitumor activity. To assess the biological effects of substituents on phenyl moieties, we also synthesized and investigated the analogous metal(II) complexes of the anion of the less bulky 1,3-diphenylpropane-1,3-dione (HLPh) ligand. The compounds [Cu(LCF3)2], [Cu(LMes)2] and ([Zn(LMes)2]) were characterized by X-ray crystallography. The [Cu(LCF3)2] crystallizes with an apical molecule of solvent (THF) and features a rare square pyramidal geometry at the Cu(II) center. The copper(II) and zinc(II) complexes of diketonate ligands, derived from the deprotonated 1,3-dimesitylpropane-1,3-dione (HLMes), adopt a square planar or a tetrahedral geometry at the metal, respectively. We evaluated the antitumor properties of the newly synthesized (Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II)) complexes against a series of human tumor cell lines derived from different solid tumors. Except for iron derivatives, cellular studies revealed noteworthy antitumor properties, even towards cancer cells endowed with poor sensitivity to the reference drug cisplatin

Exploring fluorinated and non-fluorinated β-diketonates: synthesis and biological evaluation of first-row transition metal(II) complexes for cancer treatment

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