Steroid-based anion receptors and transporters

Brotherhood, Peter R.; Davis, Anthony P.

doi:10.1039/b926225n

Cited by 176 publications

(84 citation statements)

References 66 publications

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“…Consequently, the hydrophobic-hydrophilic balance of the compound is either increased or reduced, thus modifying its self-aggregation in aqueous solution. Several papers dealing with the physicochemical properties and applications in fields such as supramolecular chemistry, biomedicine, and pharmaceutics have been reported [18,[22][23][24][25][26][27][28].…”

Section: R1mentioning

confidence: 99%

A Standard Structure for Bile Acids and Derivatives

et al. 2018

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Abstract:The crystal structures of two ester compounds (a monomer in its methyl ester form, with an amino isophthalic group, and a dimer in which the two steroid units are linked by a urea bridge recrystallized from ethyl acetate/methanol) derived from cholic acid are described. Average bond lengths and bond angles from the crystal structures of 26 monomers and four dimers (some of them in several solvents) of bile acids and esters (and derivatives) are used for proposing a standard steroid nucleus. The hydrogen bond network and conformation of the lateral chain are also discussed. This standard structure was used to compare with the structures of both progesterone and cholesterol.

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Section: R1mentioning

confidence: 99%

A Standard Structure for Bile Acids and Derivatives

et al. 2018

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“…P. Davis and co-workers have continued their work on cholapods, which have previously been shown to be very powerful anion receptors and transporters. 97 In 2011 they reported the development of smaller cholapod-like receptors based on a central trans-decalin system 171a-i, which have the advantage of smaller molecular weights and decreased lipophilicity and are therefore more ''drug-like'' molecules. 98 1 H NMR titrations showed a strong 1 : 1 interaction between the receptors and tetraethylammonium chloride, and extraction techniques were used to estimate binding affinities of >10 6 M…”

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confidence: 99%

Anion receptor chemistry: highlights from 2008 and 2009

2010

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“…As the transport activity of 3 was only weak, this raises the concern that powerful anionophores might be highly toxic and thus unsuitable for CF treatment. We have developed a range of anionophores based on powerful anion binding sites created from hydrogen bond donor groups mounted on alicyclic scaffolds (see for example Figure 4 1) 10,27 . Scaffolds include steroids 18,28,29 , trans-decalins 30,31 and substituted cyclohexanes 32 , and the common design motif is the positioning of axially-directed H-bond donors in 1,5-relationships.…”

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confidence: 99%

Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia

Valkenier

Judd³

et al. 2015

Nature Chem

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The transport of anions across cell membranes has become an important goal for supramolecular chemistry [1][2][3][4] . It is well-known that cation carriers (cationophores) can serve as antibiotics and toxins 5,6 , and it seems likely that anion carriers might also show useful biological activity. However, suitable anionophores have only recently become available 7-10 , and the nature of their biological effects is still in question. A particular hope is that anionophores might be used to replace the activity of endogenous anion channels which are missing or defective 11,2 . Such deficiencies underlie a number of medical conditions including Best disease, Startle disease, Bartter's syndrome and, most notably, the widespread lifeshortening genetic disease cystic fibrosis (CF) 12,13 .If anionophores are to be used to treat these "channelopathies", it must be shown that they can be delivered to cells in sufficient quantities to produce substantial effects, of the same order of magnitude as endogenous anion channels, and that these quantities are not toxic to the cells. However, while a wide variety of anionophores have been studied in synthetic membranes (principally large unilamellar vesicles, or LUVs), the range of systems subjected to biological investigations is still quite limited. Moreover, from the point of view of CF treatment, the results thus far have been mixed. On the positive side, a few systems have been tested in whole cells, epithelia or (in one case) genetically modified mice 14 , using electrophysiological methods such as patch-clamp and Ussing chamber, and shown to induce anion conduction without obvious toxic effects. These anionophores include synthetic 3 peptides conceptually related to natural anion channels 11,[15][16][17] , as well as the steroid-based system 1 from the authors' laboratory 18 , and other small organic molecules 14,19,20 .Less encouragingly, a number of molecules showing anion transport in LUVs have tested positive for anti-cancer cytotoxicity (potentially valuable, but incompatible with CF treatment) 8,[21][22][23][24][25] . Many of these systems, including the well-studied prodigiosin 2 26 , transport protons as well as anions 8,[21][22][23] . Intracellular acidification can lead to apoptosis 26 , so in these cases proton transport could underlie toxicity. On the other hand, a recent study on calixpyrroles 3 suggested that anion transport as such could be cytotoxic 25 . As the transport activity of 3 was only weak, this raises the concern that powerful anionophores might be highly toxic and thus unsuitable for CF treatment. Thus far the only biological testing of these "1,5-diaxial" systems has been the early study on 1, referred to above 18 . The assay involved the application of 1 to the apical membrane of oriented Madin Darby canine kidney cell (MDCK) epithelia, mounted in an Ussing chamber, and measurement of the resulting electrical current caused by Cl − transport. The methodology is well-established, but not so convenient for screening large numbers of compounds.Mor...

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Steroid-based anion receptors and transporters

Cited by 176 publications

References 66 publications

A Standard Structure for Bile Acids and Derivatives

A Standard Structure for Bile Acids and Derivatives

Anion receptor chemistry: highlights from 2008 and 2009

Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia

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