Density functional theory study of gold(III)-dithiocarbamate complexes with characteristic anticancer potentials

Lawal, Monsurat M.; Lawal, Isiaka A.; Klink, Michael J.; Tolufashe, Gideon F.; Ndagi, Umar; Kumalo, Hezekiel M.

doi:10.1016/j.jinorgbio.2020.111044

Cited by 12 publications

(7 citation statements)

References 56 publications

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“…Bulk solvent contribution to each complex gave values of −65.88, −66.33, and −67.82 kcal/mol for 1 , 2 , and 3 , respectively. These high energies show the importance of solvation in metal complexes; it redefines their electronic behavior and reshapes their geometries. , …”

Section: Resultsmentioning

confidence: 99%

“…We calculate some quantum chemical parameters of these complexes using a density functional theory (DFT) approach. The application of the DFT methods in estimating the chemical reactivity concepts of bioactive metal complexes is relevant. , Studies have shown its uses in calculating electron distribution to explore compounds’ reactivities. − We predict the potentials of these complexes as drug candidates using web-based software. The prediction guided our selection of cytochrome P450 3A4 (CYP3A4) to study the complexes’ inhibitory potency against this enzyme using our own N-layered integrated molecular orbital and molecular mechanics (ONIOM) method.…”

Section: Introductionmentioning

confidence: 99%

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Design of New Schiff-Base Copper(II) Complexes: Synthesis, Crystal Structures, DFT Study, and Binding Potency toward Cytochrome P450 3A4

et al. 2021

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We report the synthesis and crystal structures of three new copper(II) Schiff-base complexes. The complexes have been characterized by elemental analysis and Fourier transform infrared (FT-IR) and UV–visible spectroscopies. The X-ray diffraction (XRD) analysis reveals that complexes 1 and 3 crystallize in a monoclinic space group C2/c and 2 in a triclinic space group P1̅, each adopting a square planar geometry around the metal center. We use a density functional theory method to explore the quantum chemical properties of these complexes. The calculation proceeds with the three-dimensional (3D) crystal structure characterization of the complexes in which the calculated IR and UV–vis values are comparable to the experimental results. Charge distribution and molecular orbital analyses enabled quantum chemical property prediction of these complexes. We study the drug-likeness properties and binding potentials of the synthesized complexes. The in silico outcome showed that they could serve as permeability-glycoprotein (P-gp) and different cytochrome P450 substrates. Our calculations showed that the complexes significantly bind to cytochrome P450 3A4.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Design of New Schiff-Base Copper(II) Complexes: Synthesis, Crystal Structures, DFT Study, and Binding Potency toward Cytochrome P450 3A4

et al. 2021

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“…Despite the difference in mechanism, caplain is involved in the apoptotic cell death process of dithiocarbamate of both zinc and copper [151]. Dithiocarbamate complexes of trivalent gold have also been found to be effective against cancer cells [152]. Similarly, derivatives of benzoxazole with dithiocarbamate moieties were found to be active in the treatment of breast cancer [153].…”

Section: Anticancer Application Of Dithiocarbamate Compoundsmentioning

confidence: 99%

The Versatility in the Applications of Dithiocarbamates

Ajiboye

Marzouki

Onwudiwe

2022

IJMS

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Dithiocarbamate ligands have the ability to form stable complexes with transition metals, and this chelating ability has been utilized in numerous applications. The complexes have also been used to synthesize other useful compounds. Here, the up-to-date applications of dithiocarbamate ligands and complexes are extensively discussed. Some of these are their use as enzyme inhibitor and treatment of HIV and other diseases. The application as anticancer, antimicrobial, medical imaging and anti-inflammatory agents is examined. Moreover, the application in the industry as vulcanization accelerator, froth flotation collector, antifouling, coatings, lubricant additives and sensors is discussed. The various ways in which they have been employed in synthesis of other compounds are highlighted. Finally, the agricultural uses and remediation of heavy metals via dithiocarbamate compounds are comprehensively discussed.

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“…The reactivity and selectivity of gold(III) complexes with dithiocarbamate ligands were investigated computationally (Figure 18, structures 40a, 40b, 41a, 41b) [100], revealing the importance of interatomic sulfur-halogen coordination in the stabilization of the metallic scaffold. Reactivity and selectivity toward TrxR were found to be related to the presence of charge transfer effects--either interatomic, within the gold(III) complex, or intermolecular, between the metal complex and TrxR enzyme.…”

Section: Au(iii) Complexes With Cyclometalated Ligandsmentioning

confidence: 99%

“…Another relevant aspect in the computational investigation of Au(I) and Au(III) metallodrugs is represented by the viability of either Au(III)→Au(I) or Au(I)→Au(0) reduction processes. Indeed, due to the possible reductive elimination affecting either Au(I) or Au(III) scaffolds, many metallodrugs are coordinated by ligands that provide for redox stabilization [95,[99][100][101][102][103]. DFT and, more generally, ab initio approaches can be potentially employed to probe the redox stability of gold metallodrugs, even before and after the target metalation has occurred.…”

Section: Challenges Strengths and Limitations Of Current Computational Approachesmentioning

confidence: 99%

Computational Studies of Au(I) and Au(III) Anticancer MetalLodrugs: A Survey

et al. 2021

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Owing to the growing hardware capabilities and the enhancing efficacy of computational methodologies, computational chemistry approaches have constantly become more important in the development of novel anticancer metallodrugs. Besides traditional Pt-based drugs, inorganic and organometallic complexes of other transition metals are showing increasing potential in the treatment of cancer. Among them, Au(I)- and Au(III)-based compounds are promising candidates due to the strong affinity of Au(I) cations to cysteine and selenocysteine side chains of the protein residues and to Au(III) complexes being more labile and prone to the reduction to either Au(I) or Au(0) in the physiological milieu. A correct prediction of metal complexes’ properties and of their bonding interactions with potential ligands requires QM computations, usually at the ab initio or DFT level. However, MM, MD, and docking approaches can also give useful information on their binding site on large biomolecular targets, such as proteins or DNA, provided a careful parametrization of the metal force field is employed. In this review, we provide an overview of the recent computational studies of Au(I) and Au(III) antitumor compounds and of their interactions with biomolecular targets, such as sulfur- and selenium-containing enzymes, like glutathione reductases, glutathione peroxidase, glutathione-S-transferase, cysteine protease, thioredoxin reductase and poly (ADP-ribose) polymerase 1.

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Density functional theory study of gold(III)-dithiocarbamate complexes with characteristic anticancer potentials

Cited by 12 publications

References 56 publications

Design of New Schiff-Base Copper(II) Complexes: Synthesis, Crystal Structures, DFT Study, and Binding Potency toward Cytochrome P450 3A4

Design of New Schiff-Base Copper(II) Complexes: Synthesis, Crystal Structures, DFT Study, and Binding Potency toward Cytochrome P450 3A4

The Versatility in the Applications of Dithiocarbamates

Computational Studies of Au(I) and Au(III) Anticancer MetalLodrugs: A Survey

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