Synthesis and biological evaluation of allylated mono-carbonyl analogues of curcumin (MACs) as anti-cancer agents for cholangiocarcinoma.
A series of new allylated mono-carbonyl curcumin analogues (MACs) were designed and synthesized. In vitro cytotoxic activities of allylated MACs 6a-h together with previously reported analogues 4a-i and 7a-e, were tested against human cholangiocarcinoma cell lines including HUCCA, QBC-939 and RBE. Of all the compounds tested, 6c exhibited potent in vitro antiproliferative activity against the three tested cancer cell lines with IC50values of 8.7, 9.3 and 8.9μM, respectively. Cell cycle analysis showed that 6c inhibited cell proliferation due to G2/M arrest. Furthermore, mechanistic studies revealed that 6c dose-dependently increased the level of Bax and inhibited the expression of Bcl-2, to induce cancer cell apoptosis. Taken together, this work provides a novel series of anti-cancer candidates for the treatment of cholangiocarcinoma.
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
Chenyu
C
Qiu
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Yan
Y
Hu
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
Ke
K
Wu
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
Ke
K
Yang
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
Nan
N
Wang
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
Yue
Y
Ma
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
Heping
H
Zhu
The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Yi
Y
Zhang
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China; The Sixth Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Yunfang
Y
Zhou
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China; College of Life Sciences, Huzhou University, Huzhou, Zhejiang 313000, China.
Chao
C
Chen
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
Shanshan
S
Li
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
Lili
L
Fu
The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: wzzhangxiuhua@126.com.
Xiuhua
X
Zhang
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China. Electronic address: lzgcnu@163.com.
Zhiguo
Z
Liu
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000473:pathology; D003474:Curcumin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D003474:Curcumin
Chemical stability; Cholangiocarcinoma; Drug design; Mono-carbonyl curcumin analogues