Synthesis and Structure-Activity Relationships of Amino Acid Conjugates of Cholanic Acid as Antagonists of the EphA2 Receptor

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 …