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Design and synthesis of iodocarborane-containing ligands with high affinity and selectivity toward ERβ.

Abstract：

:The selectivity and the binding affinity of previously reported carborane-containing ligands 2 and 3 toward ERβ remains to be optimized. To improve their biological profiles, a series of iodinated carboranyl phenol derivatives (4-6) were designed and synthesized as prospective ERβ-selective ligands with high affinity. Several iodinated carboranyl phenols showed high relative binding affinity (RBA) values for both ERs, and especially for ERβ, due to suitable hydrophobic interactions of the iodine atoms with the hydrophobic amino acid residues of the ERβ ligand-binding domains. Among these derivatives, 9,10-diiodo-m-carborane 5f exhibited a more than 100% increase of the RBA values toward ERβ, a 14-fold increased selectivity for ERβ over ERα, and ER-agonistic activity in MCF-7 cell proliferation assays.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Ohta K,Ogawa T,Endo Y

doi

10.1016/j.bmcl.2017.07.053

subject

Has Abstract

pub_date

2017-09-01 00:00:00

pages

4030-4033

issue

17

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(17)30760-6

journal_volume

27

pub_type

杂志文章

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