Synthesis, Crystal Structure, and Computational Methods of Vanadium and Copper Compounds as Potential Drugs for Cancer Treatment

Abstract

Transition metal-based compounds have shown promising uses as therapeutic agents. Among their unique characteristics, these compounds are suitable for interaction with specific biological targets, making them important potential drugs to treat various diseases. Copper compounds, of which Casiopeinas® are an excellent example, have shown promising results as alternatives to current cancer therapies, in part because of their intercalative properties with DNA. Vanadium compounds have been extensively studied for their pharmacological properties and application, mostly in diabetes, although recently, there is a growing interest in testing their activity as anti-cancer agents. In the present work, two compounds, [Cu(Metf)(bipy)Cl]Cl·2H2O and [Cu(Impy)(Gly)(H2O)]VO3, were obtained and characterized by visible and FTIR spectroscopies, single-crystal X-ray diffraction, and theoretical methods. The structural and electronic properties of the compounds were calculated through the density functional theory (DFT) using the Austin–Frisch–Petersson functional with dispersion APFD, and the 6-311 + G(2d,p) basis set. Non-covalent interactions were analyzed using Hirshfeld surface analysis (HSA) and atom in molecules analysis (AIM). Additionally, docking analysis to test DNA/RNA interactions with the Casiopeina-like complexes were carried out. The compounds provide metals that can interact with critical biological targets. In addition, they show interesting non-covalent interactions that are responsible for their supramolecular arrangements.

L-Citrullinato-Bipyridine and L-Citrullinato-Phenanthroline Mixed Copper Complexes: Synthesis, Characterization and Potential Anticancer Activity

“…On the other hand, in both complexes, the axial position of the distorted square pyramidal center is occupied by one H 2 O molecule, which is coordinated with Cu1 through O3, with Cu1-O3 distances of 2.278 and 2.280 Å for complexes 1 ′ and 2 ′ , respectively. Similar values of 3.019-3.030 Å for D, L-Citrullinatobipyridine complex [24]; 2.221-2.308 Å for L-Glutamine and phenanthroline complex [54]; and 2.756 Å for Metformin and bipyridine complex [67], have been calculated for complexes with H 2 O molecule in the axial position coordinated with Cu(II). In Figure 5b, the molecular electrostatic potential (MEP) was mapped on the total electronic density in a range of −2.0 × 10 −2 (red regions) to 2.0 × 10 −2 (blue regions) of electronic density, with an isovalue = 0.0004 a.u.…”

In Vitro and In Vivo Biological Activities of Dipicolinate Oxovanadium(IV) Complexes

“…Vanadium compounds have been widely investigated due to a broad application in catalysis − and a wide range of pharmacological properties. − In the area of medicinal applications, the exploration of vanadium-based compounds has been focused on their insulin-mimetic properties, − ,− anticancer activities, − ,− antibacterial action, ,,,− and effects on enzymes. ,,, In particular, bis(ethylmaltolato)oxidovanadium(IV) (BEOV) entered the phase IIa clinical trials as an antidiabetic agent and its improved pharmacokinetics relative to vanadyl sulfate was evidenced. − Vanadocene dichloride, (η 5 -C 5 H 5 ) 2 VCl 2 (C 5 H 5 = cyclopentadienyl), was demonstrated to have antitumor effects on a wide spectrum of cancer cells, including testicular cancer, leukemia, breast cancer, glioblastoma, and colon cancer. − ,− Among oxidovanadium(IV) derivatives, special attention has been devoted to bis(4,7-dimethyl-1,10-phenanthroline)-sulfatooxidovanadium(IV) (Metvan), which was found to induce apoptosis in leukemia, multiple myeloma, and solid tumors such as breast, prostate, testis, and glioblasto...…”

“…Vanadium compounds have been widely investigated due to a broad application in catalysis 1 − 9 and a wide range of pharmacological properties. 10 − 19 In the area of medicinal applications, the exploration of vanadium-based compounds has been focused on their insulin-mimetic properties, 11 − 15 , 20 − 25 anticancer activities, 11 − 19 , 26 − 40 antibacterial action, 12 , 14 , 15 , 41 − 43 and effects on enzymes. 12 , 14 , 15 , 44 In particular, bis(ethylmaltolato)oxidovanadium(IV) (BEOV) entered the phase IIa clinical trials as an antidiabetic agent and its improved pharmacokinetics relative to vanadyl sulfate was evidenced.…”

Tris(2-Pyridylmethylamine)V(O)2 Complexes as Counter Ions of Diprotonated Decavanadate Anion: Potential Antineoplastic Activity

“…Recently, our research group has been involved in the synthesis and experimental and theoretical characterization of decavanadates and cyclo-tetravanadates as potential metallo-prodrugs for the treatment of diabetes and cancer ( Sánchez-Lara et al, 2015 ; Sánchez-Lara et al, 2019 ; Sánchez-Lara et al, 2021 ), ( Martínez-Valencia et al, 2020 ), ( Martínez-Valencia et al, 2020 ), ( Corona-Motolinia et al, 2020 ), and ( García-García et al, 2021 ). We attempted to synthesize a protonated tris(2-pyridoniummehtyl)amine decavanadate to find new candidates under mild hydrothermal conditions.…”