TY - JOUR
T1 - Design, synthesis and antitumor activity of triterpenoid pyrazine derivatives from 23-hydroxybetulinic acid
AU - Zhang, Hengyuan
AU - Wang, Yiwei
AU - Zhu, Peiqing
AU - Liu, Jie
AU - Xu, Shengtao
AU - Yao, Hequan
AU - Jiang, Jieyun
AU - Ye, Wencai
AU - Wu, Xiaoming
AU - Xu, Jinyi
N1 - Publisher Copyright:
© 2015 Elsevier Masson SAS.
PY - 2015/6/5
Y1 - 2015/6/5
N2 - Pyrazine-fused 23-hydroxybetulinic acid was synthesized by introducing a pyrazine ring between C-2 and C-3 position and further modifications were carried out by substitution of C-28 carboxyl group by ester and amide linkage to enhance the antitumor activity. The biological screening results showed that all of the derivatives exhibited more significant antiproliferative activity than the parent compound. In particular compound 12a exhibited the most potent activity with IC50 values of 3.53 μM, 4.42 μM and 5.13 μM against cell lines SF-763, B16 and Hela, respectively. In the preliminary mechanism study, 12a caused cell arrest in G1 phase and significantly induced apoptosis of B16 cells in a dose-dependent manner. Furthermore, the in vivo antitumor activity of 12a was validated (tumor inhibitory ratio of 55.6% and 62.7%, respectively) in mice with H22 liver cancer and B16 melanoma.
AB - Pyrazine-fused 23-hydroxybetulinic acid was synthesized by introducing a pyrazine ring between C-2 and C-3 position and further modifications were carried out by substitution of C-28 carboxyl group by ester and amide linkage to enhance the antitumor activity. The biological screening results showed that all of the derivatives exhibited more significant antiproliferative activity than the parent compound. In particular compound 12a exhibited the most potent activity with IC50 values of 3.53 μM, 4.42 μM and 5.13 μM against cell lines SF-763, B16 and Hela, respectively. In the preliminary mechanism study, 12a caused cell arrest in G1 phase and significantly induced apoptosis of B16 cells in a dose-dependent manner. Furthermore, the in vivo antitumor activity of 12a was validated (tumor inhibitory ratio of 55.6% and 62.7%, respectively) in mice with H22 liver cancer and B16 melanoma.
KW - 23-Hydroxybetulinic acid
KW - Antitumor activity
KW - Apoptosis
KW - Pyrazine
KW - Triterpenoid
UR - http://www.scopus.com/inward/record.url?scp=84929309818&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929309818&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2015.04.057
DO - 10.1016/j.ejmech.2015.04.057
M3 - Article
C2 - 25984840
AN - SCOPUS:84929309818
SN - 0223-5234
VL - 97
SP - 235
EP - 244
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
M1 - 7872
ER -
