Carborane‐Based Carbonic Anhydrase Inhibitors

Brynda, J.; Mäder, P.; Šícha, Václav; Fábry, Milan; Poncová, Kristýna; Bakardiev, Mario; Grüner, Bohumı́r; Cígler, Petr; Řezáčová, P.

doi:10.1002/anie.201307583

Cited by 97 publications

(80 citation statements)

References 23 publications

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“…13,16 The reasons are their low toxicity, metabolic stability and their ability to participate in various unique noncovalent interactions. 16,17 Structural details about their binding are only known for a few proteins -HIV-1 protease, 18 dihydrofolate reductase 19 (DHFR), carbonic anhydrase 20,21 and vitamin D receptor. 16,17 Structural details about their binding are only known for a few proteins -HIV-1 protease, 18 dihydrofolate reductase 19 (DHFR), carbonic anhydrase 20,21 and vitamin D receptor.…”

Section: Introductionmentioning

confidence: 99%

The properties of substituted 3D-aromatic neutral carboranes: the potential for σ-hole bonding

Fanfrlík

Lepšı́k

et al. 2015

Phys. Chem. Chem. Phys.

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The calculated properties of substituted carboranes such as dipole moment, polarisability, the magnitude of the σ-hole and the desolvation free energy are compared with these properties in comparable aromatic and cyclic aliphatic organic compounds. Dispersion and charge transfer energies are similar. However, the predicted strength of the halogen bonds with the same electron donor (based on the magnitude of the σ-hole) is larger for neutral C-vertex halogen-substituted carboranes than for their organic counterparts. Furthermore, the desolvation penalties of substituted carboranes are smaller than those of the corresponding organic compounds, which should further strengthen the halogen bonds of the former in the solvent. It is predicted that substituted carboranes have the potential to form stronger halogen bonds than comparable aromatic hydrocarbons, which will be even more pronounced in the medium. This theoretical study thus lays ground for the rational engineering of halogen bonding in inorganic crystals as well as in biomolecular complexes.

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Section: Introductionmentioning

confidence: 99%

The properties of substituted 3D-aromatic neutral carboranes: the potential for σ-hole bonding

Fanfrlík

Lepšı́k

et al. 2015

Phys. Chem. Chem. Phys.

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“…Although their introduction into inhibitors has yielded promising bio-active compounds, these nido -carbaboranyl derivatives have not yet proved to be superior to the respective phenyl or adamantyl analogues. [5] …”

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confidence: 99%

nido‐Dicarbaborate Induces Potent and Selective Inhibition of Cyclooxygenase‐2

Neumann

Sárosi

et al. 2015

ChemMedChem

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Carbaboranes are increasingly studied as pharmacophores, particularly as replacements for aromatic systems. However, especially ortho-carbaborane is prone to degradation of the cluster, which hampers biological application. This study demonstrates that deboronation of the cluster may not only lead to a more active analogue but can also improve the solubility and stability of a carbaborane-containing inhibitor. Notably, introduction of a nido-dicarbaborate cluster into the cyclooxygenase (COX) inhibitor indomethacin results in a remarkably increased inhibitory potency and selectivity for COX-2 relative to the respective phenyl analogue. The first crystal structure of a carbaborane-containing inhibitor bound to COX-2 further reveals a novel binding mode for the inhibitor that is strikingly different from that of indomethacin. These results indicate that nido-dicarbaborate is a promising pharmacophore exhibiting properties which are also highly beneficial for its introduction into other inhibitor classes.

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“…The first attempts to use carboranes as a pharmacophore have been initiated by Endo and coworkers, who introduced the 1-(4-hydroxyphenyl)carborane core as a steroidal framework [8,9]. Since their reports, various compounds have been synthesized based on the carborane pharmacophore strategy including folic acid analogs [10], antifolates [11], flufenamic acid and diflunisal analogs [12], aspirin and indomethacin analogs [13,14], nicotinamide phosphoribosyltranferase inhibitors [15], carbonic anhydrase inhibitors [16], purinergic P2X 7 receptor antagonists [17], combretastatin analogs [18], and manassantin analogs [19].…”

Section: Introductionmentioning

confidence: 99%