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Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII.

Abstract：

:The transmembrane isoforms of carbonic anhydrase (hCA IX and XII) have been shown to be linked to carcinogenesis and their inhibition to arrest primary tumor and metastases growth. In this paper, we present a new class of C-glycosides incorporating the methoxyaryl moiety, that was designed to selectively target and inhibit the extracellular domains of the cancer-relevant CA isozymes. The glycosides have been prepared by aldol reaction of glycosyl ketones with the appropriate aromatic aldehydes. We also present the inhibition profile of our new glycomimetics, against four isozymes of carbonic anhydrase comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (tumor associated isozymes). In this study, per-O-acetylated glycoside 4, 6 and deprotected compounds 7, 9, 10 and 12 were identified as potent and highly selective inhibitors of hCA IX and XII. These results confirm that attaching carbohydrate moieties to CA methoxyaryl pharmacophore improves and enhances its inhibitory activity. These CA inhibitors have developmental potential to selectively target cancer cells, leading to cell death.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Riafrecha LE,Rodríguez OM,Vullo D,Supuran CT,Colinas PA

doi

10.1016/j.bmc.2014.07.052

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

5308-14

issue

19

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(14)00576-8

journal_volume

22

pub_type

杂志文章

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