Metal Complexes of Sulfonamides as Dual Carbonic Anhydrase Inhibitors

Ilies, Marc A.

doi:10.1002/9780470508169.ch21

Cited by 3 publications

(4 citation statements)

References 76 publications

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“…Sulfonamides are versatile chelating ligands and, depending on their structure, they can act as mono‐, bi‐ or tridentate donor systems to transition metal ions . The coordination complexes of different clinically used sulfonamides with Ag I , Co II , Ni II , Cu II , and Zn II have been evaluated for their biological properties . In many examples, the enzyme inhibitory activity of these metal complexes was better than that of their ligands alone, possibly due to synergistic effects between the metal ion and the sulfonamide by interacting with different areas of the active site of the enzyme .…”

Section: Introductionmentioning

confidence: 89%

Organoruthenium and Organoosmium Complexes of 2‐Pyridinecarbothioamides Functionalized with a Sulfonamide Motif: Synthesis, Cytotoxicity and Biomolecule Interactions

et al. 2018

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Anticancer‐active RuII–η6‐p‐cymene complexes of bioactive 2‐pyridinecarbothioamide ligands have been shown to have high selectivity for plectin and can be administered orally. Reported herein is the functionalization of a 2‐pyridinecarbothioamide with a sulfonamide group and its conversion into M–η6‐p‐cymene complexes (M = Ru, Os). The presence of a sulfonamide moiety in many organic drugs and metal complexes endows these agents with interesting biological properties and can transform the latter into multi‐targeted agents. The compounds were characterized with standard methods and the in vitro anticancer activity data was compared with studies on the hydrolytic stability of the complexes and their reactivity to small biomolecules. A molecular modeling study revealed plausible modes of binding of the complexes in the catalytic pocket of carbonic anhydrase II.

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Section: Introductionmentioning

confidence: 89%

Organoruthenium and Organoosmium Complexes of 2‐Pyridinecarbothioamides Functionalized with a Sulfonamide Motif: Synthesis, Cytotoxicity and Biomolecule Interactions

et al. 2018

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“…[26–28] These four and other protonation states can coexist as determined by several factors. [28] It should be noted that the protonation state of AZM in complex hCAII was revealed in a very interesting recent experiment employing the technique of neutron diffraction. [26] State (AZM-1a) of Fig.…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics study of human carbonic anhydrase II in complex with Zn2+ and acetazolamide on the basis of all-atom force field simulations

Wambo

Chen

McHardy

et al. 2016

Biophysical Chemistry

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Human carbonic anhydrase II (hCAII) represents an ultimate example of the perfectly efficient metalloenzymes, which is capable of catalyzing the hydration of carbon dioxide with a rate approaching the diffusion controlled limit. Extensive experimental studies of this physiologically important metalloprotein have been done to elucidate the fundamentals of its enzymatic actions: what residues anchor the Zn2+ (or another divalent cation) at the bottom of the binding pocket; how the relevant residues work concertedly with the divalent cation in the reversible conversions between CO2 and HCO3−, what are the protonation states of the relevant residues and acetazolamide, an inhibitor complexed with hCAII, etc. In this article, we present a detailed computational study on the basis of the all-atom CHARMM force field where Zn2+ is represented with a simple model of divalent cation using the transferrable parameters available from the current literature. We compute the hydration free energy of Zn2+, the characteristics of hCAII-Zn2+ complexation, and the absolute free energy of binding acetazolamide to the hCAII-Zn2+ complex. In each of these three problems, our computed results agree with the experimental data within the known margin of error without making any case-by-case adjustments to the parameters. The quantitatively accurate insights we gain in this all-atom molecular dynamics study should be helpful in the search and design of more specific inhibitors of this and other carbonic anhydrases.

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“…Their activity, too, increases on complexation with metal ions. The most significant part of such metal based drug chemistry is, the ability of metal ions to bind in vivo with proteins and peptides [2]. Simple sulfonamides have been observed to attract much attention into this emerging area of metal based sulfa drugs, initially stimulated by the successful introduction of metal complexes of sulfadiazine to prevent bacterial infections [3].…”

Section: Introductionmentioning

confidence: 99%

“…Selected bond distances (Å), bond angles (°), and torsional angles (°) for ligand (1) and complex(2).Symmetry…”

mentioning

confidence: 99%

Crystal structure, spectroscopy and theoretical studies of p-cyanobenzenosulfonamide and a Cu(II) complex

Camí

Villalba

Colinas

et al. 2012

Journal of Molecular Structure

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Metal Complexes of Sulfonamides as Dual Carbonic Anhydrase Inhibitors

Cited by 3 publications

References 76 publications

Organoruthenium and Organoosmium Complexes of 2‐Pyridinecarbothioamides Functionalized with a Sulfonamide Motif: Synthesis, Cytotoxicity and Biomolecule Interactions

Organoruthenium and Organoosmium Complexes of 2‐Pyridinecarbothioamides Functionalized with a Sulfonamide Motif: Synthesis, Cytotoxicity and Biomolecule Interactions

Molecular dynamics study of human carbonic anhydrase II in complex with Zn2+ and acetazolamide on the basis of all-atom force field simulations

Crystal structure, spectroscopy and theoretical studies of p-cyanobenzenosulfonamide and a Cu(II) complex

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