Ternary Copper Complex of L-Glutamine and Phenanthroline as Counterions of Cyclo-Tetravanadate Anion: Experimental–Theoretical Characterization and Potential Antineoplastic Activity

Abstract

Over the last decade, therapeutic metallodrugs have become substantially effective in the treatment of cancer. Thus, developing new effective anticancer drugs is a significant research area against the continuing increase in cancers worldwide. In the search for heterobimetallic prodrugs containing V/Cu, a new cyclo-tetravanadate was synthesized and characterized by UV-visible and FTIR spectroscopies and single-crystal X-ray diffraction. L-Glutamine and 1,10-phenanthroline allow the crystallization of [Cu(L-Gln)(phen)(H2O)]4[V4O12]∙8(H2O) (1), in which the cyclo-tetravanadate acts as a free anion. Density functional theory (DFT) calculations were carried out to characterize the frontier molecular orbitals and molecular electrostatic potential. Global reactivity indexes were calculated and analyzed to give insight into the cyclo-tetravanadate anion and complex counterions interactions. Also, using Bader’s theory of atoms in molecules (AIM), non-covalent interactions were analyzed. Docking analysis with the Casiopeina-like complex resulting from the hydrolysis of compound 1 provided insights into these complex potential anticancer activities by interacting with DNA/tRNA via H-bonds and hydrophobic interactions. The release of both components could act together or separately, acting as prodrugs with potential dual antineoplastic activities.

Bis-Citrullinato Copper(II) Complex: Synthesis, Crystal Structure, and Non-Covalent Interactions

“…The CuO 4 N 2 sphere is formed by two O1 atoms from the carboxylate groups of ligands A and B, two N1 atoms belonging to amino groups of the same ligands, and two O3 atoms of amide groups of two different ligands (Figure 1b). The coordination sphere's deformation results from the high Jahn-Teller effect around de d-orbitals of Cu(II) in octahedral geometry, which tend to split degenerate energy levels [48]; the basal positions are occupied by two Cu-N and two Cu-O bonds with distances in the range of 1.952(8)-1.978(8) Å and 1.951(8)-1.961(7) Å, respectively, similar to other reported structures [30,[49][50][51]. According to the literature, the Cu-O bond distances at the apical positions range from 2.4 to 2.8 Å, corresponding to electrostatic interactions [52].…”

“…As part of our attempts to generate possible metallodrugs based on Casiopeina ® analogs, we have previously reported copper-mixed complexes incorporating lysine, ornithine, and glutamine, and docking studies reveal their interaction with DNA/RNA [28][29][30]. Here we report the synthesis and experimental-theoretical characterization of the [Cu(Citr) 2 ] complex and its crystal structure for the first time.…”

N-Naphthoyl Thiourea Derivatives: An Efficient Ultrasonic-Assisted Synthesis, Reaction, and In Vitro Anticancer Evaluations

“…The stark cytotoxic activities of thiourea derivatives against various types of cancers make them valuable structural motifs. − Likewise, to have an access to novel therapeutic metal-based anticancer drugs with profound cytotoxicity, it is frequent to combine pharmacophores with metals. Accordingly, various metal complexes exhibited potent antiproliferative activities and are in clinical use as anticancer drugs. , In the same context, copper complexes are of paramount importance as anticancer agents revealing promising in vitro and in vivo antiproliferative activities. , Therefore, combining thiourea pharmacophores with Cu­(II) became a very favorable approach for developing compounds with antitumor activities. , With the N -naphthoyl thiourea library in hand, attention was now turned toward testing it for cytotoxicity against a range of cancer cell lines. In addition, the antiproliferative activity of Cu-complex 11 will be examined.…”

“…53,54 In the same context, copper complexes are of paramount importance as anticancer agents revealing promising in vitro and in vivo antiproliferative activities. 55,56 Therefore, combining thiourea pharmacophores with Cu(II) became a very favorable approach for developing compounds with antitumor activities. 57,58 With the Nnaphthoyl thiourea library in hand, attention was now turned toward testing it for cytotoxicity against a range of cancer cell lines.…”

Interaction of copper potential metallodrugs with TMPRSS2: A comparative study of docking tools and its implications on COVID-19

“…The optimized molecular structures of the cationic complexes were calculated using the DFT method with the functional mPW1PW91 ( Adamo and Barone, 1998 ) from the crystal structures already reported ( Tovar-Tovar et al, 2004 ; Patra et al, 2009 ; García-Ramos et al, 2014 ; Martínez-Valencia et al, 2020 ; Rodrigues et al, 2020 ; Corona-Motolinia et al, 2021 ; Sánchez-Lara et al, 2021 ; Ramírez-Contreras et al, 2022 ) or modeled from them using Spartan'20 (Wavefunction Inc.). The basis set 6-311G(d) ( Krishnan et al, 1980 ) was used for C, N, and O atoms, and 6-31G ( Ditchfield et al, 1971 ) was used for H atoms.…”