Novel NO-releasing derivatives of betulinic acid with antitumor activity

Thirteen novel NO-releasing derivatives of betulinic acid (BA) bearing two types of NO-donors (nitrates and furoxans) were synthesized and evaluated for their antitumor activity. The results showed that furoxan-based derivatives exhibited higher antitumor activity than nitrate-based derivatives, with compounds 11a and 11b displaying promising potency against B16 cell lines and HepG2 cell lines (IC50 < 1 μmol/L). We supposed that NO-releasing amount of these derivatives which can be detected by Griess method may contribute more to their antitumor activity. As a result, furoxan-based derivatives released larger amount of NO than that of nitrate-based derivatives, which partially explained the higher anti-tumor activity of the former.

The results indicated that the amount of NO released by the furoxan-based derivatives (11a–b) of BA is generally higher than that of nitrate-based derivatives (4a–d), which is consistent with the anti-tumor activity of the corresponding derivatives. Especially, compounds 11a and 11b displayed the most promising potency against B16 cell lines and HepG2 cell lines (IC50 < 1 μmol/L).Figure optionsDownload as PowerPoint slide