DFT calculations of copper complexes mimicking superoxide dismutase and docking studies and molecular dynamics of the transition metal complex binding to serum albumin

Article

Author: Silva, Talis Uelisson da ; Lima, Camilo Henrique da Silva ; Machado, Sérgio de Paula ; Silva, Everton Tomaz ; Albuquerque, Magaly Girão

Superoxide dismutase (SOD) is a metalloenzyme whose antioxidant activity is mimicked by some transition metal complexes, and such ability can be added in proteins such as the bovine serum albumin (BSA), creating a hybrid protein. In this work, density functional theory (DFT) calculations of three Cu(II)-complexes of general formula [CuL₂phen] (phen = phenanthroline; C1, L = mefenamate; C2, L = tolfenamate; C3, L = flufenamate) with SOD-like activity, and docking and molecular dynamics (MD) simulations of these complexes with the BSA were performed. The DFT calculations revealed that the complex reduction involves Cu(II) → Cu(I) reduction, the theoretical electron affinity (EA) correlated with the SOD-like activity (IC₅₀), and the contribution of the phenanthroline ligand and the metal in LUMO it's related with the complex-protein interaction (K_VS). The docking and MD simulations revealed the binding site of the complexes in BSA and the residues involved in the binding. The stability of the Cu(II) and Cu(I) forms of the complexes in the site indicated that the catalysis promoted by these complexes occurs in the same region of the BSA and that their mimetic activity can be incorporated into BSA, creating a hybrid protein (BSA with SOD activity)Communicated by Ramaswamy H. Sarma.

24 Apr 2023·Nucleic acids research

Unusual enantioselective cytoplasm-to-nucleus translocation and photosensitization of the chiral Ru(II) cationic complex via simple ion-pairing with lipophilic weak acid counter-anions.

Article

Author: Huang, Chun-Hua ; Zhu, Ben-Zhan ; Chao, Xi-Juan ; Yan, Zhu-Ying ; Tang, Miao ; Huang, Rong ; Li, Yan

Targeted and enantioselective delivery of chiral diagnostic-probes and therapeutics into specific compartments inside cells is of utmost importance in the improvement of disease detection and treatment. The classical DNA 'light-switch' ruthenium(II)-polypyridyl complex, [Ru(DIP)2(dppz)]Cl2 (DIP = 4,7-diphenyl-1,10-phenanthroline, dppz = dipyridophenazine) has been shown to be accumulated only in the cytoplasm and membrane, but excluded from its intended nuclear DNA target. In this study, the cationic [Ru(DIP)2(dppz)]2+ is found to be redirected into live-cell nucleus in the presence of lipophilic 3,5-dichlorophenolate or flufenamate counter-anions via ion-pairing mechanism, while maintaining its original DNA recognition characteristics. Interestingly and unexpectedly, further studies show that only the Δ-enantiomer is selectively translocated into nucleus while the Λ-enantiomer remains trapped in cytoplasm, which is found to be mainly due to their differential enantioselective binding affinities with cytoplasmic proteins and nuclear DNA. More importantly, only the nucleus-relocalized Δ-enantiomer can induce obvious DNA damage and cell apoptosis upon prolonged visible-light irradiation. Thus, the use of Δ-enantiomer can significantly reduce the dosage needed for maximal treatment effect. This represents the first report of enantioselective targeting and photosensitization of classical Ru(II) complex via simple ion-pairing with suitable weak acid counter-anions, which opens new opportunities for more effective enantioselective cancer treatment.

01 Apr 2018·Molecular and Cellular BiochemistryQ3 · BIOLOGY

Unprecedented anticancer activities of organorhenium sulfonato and carboxylato complexes against hormone-dependent MCF-7 and hormone-independent triple-negative MDA-MB-231 breast cancer cells

Q3 · BIOLOGY

Article

Author: Winstead, Angela ; Odebode, Tijesunimi ; Ho, Douglas M ; Azemati, Samira ; Stevenson, Monet ; Shaw, Roosevelt ; Tadesse, Solomon ; Hinton, Tiara V ; Powell, Brent V ; Golen, James A ; McCarthy, Pumtiwitt ; Rheingold, Arnold L ; Zavalij, Peter Y ; Parnell, Sabreea ; Wachira, James M ; Barfield, Alexis ; Zhang, Yongchao ; Pramanik, Saroj K ; Chen, Chao ; Ghimire, Sujan ; Giri, Dipak ; Krause, Jeanette A ; Olczak, Pola ; Mandal, Santosh K ; Wilder, Paul T ; Banerjee, Hirendra N ; Weber, David J

Cisplatin and other metal-based drugs often display side effects and tumor resistance after prolonged use. Because rhenium-based anticancer complexes are often less toxic, a novel series of organorhenium complexes were synthesized of the types: XRe(CO)₃Z (X = α-diimines and Z = p-toluenesulfonate, 1-naphthalenesulfonate, 2-naphthalenesulfonate, picolinate, nicotinate, aspirinate, naproxenate, flufenamate, ibuprofenate, mefenamate, tolfenamate, N-acetyl-tryptophanate), and their biological properties were examined. Specifically, in hormone-dependent MCF-7 and hormone-independent triple-negative MDA-MB-231 breast cancer cells, the p-toluenesulfonato, 1-naphthalenesulfonato, 2-naphthalenesulfonato, picolinato, nicotinato, acetylsalicylato, flufenamato, ibuprofenato, mefenamato, and N-acetyl-tryptophanato complexes were found to be far more potent than conventional drug cisplatin. DNA-binding studies were performed in each case via UV-Vis titrations, cyclic voltammetry, gel electrophoresis, and viscosity, which suggest DNA partial intercalation interaction, and the structure-activity relationship studies suggest that the anticancer activities increase with the increasing lipophilicities of the compounds, roughly consistent with their DNA-binding activities.

100 Deals associated with Flufenamate Aluminum

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KEGG	Wiki	ATC	Drug Bank
D03254	-	M01AG03	-

R&D Status

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Indication	Country/Location	Organization	Date
Analgesia	JP	Taisho Pharmaceutical Co., Ltd.	01 Aug 1967
Fever	JP	Taisho Pharmaceutical Co., Ltd.	01 Aug 1967
Inflammation	JP	Taisho Pharmaceutical Co., Ltd.	01 Aug 1967

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