Synthesis and structure-activity relationships of amino acid conjugates of cholanic acid as antagonists of the EphA2 receptor.

ABSTRACT: The Eph-ephrin system plays a critical role in tumor growth and vascular functions during carcinogenesis. We had previously identified cholanic acid as a competitive and reversible EphA2 antagonist able to disrupt EphA2-ephrinA1 interaction and to inhibit EphA2 activation in prostate cancer cells. Herein, we report the synthesis and biological evaluation of a set of cholanic acid derivatives obtained by conjugation of its carboxyl group with a panel of naturally occurring amino acids with the aim to improve EphA2 receptor inhibition. Structure-activity relationships indicate that conjugation of cholanic acid with linear amino acids of small size leads to effective EphA2 antagonists whereas the introduction of aromatic amino acids reduces the potency in displacement studies. The b-alanine d

SUBMITTER: Russo S 

PROVIDER: S-EPMC6270184 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature