2. Academic Validation
  3. Synthesis and anticancer activity of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives bearing chromone moiety

Synthesis and anticancer activity of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives bearing chromone moiety

  • Bioorg Med Chem. 2016 Aug 15;24(16):3862-9. doi: 10.1016/j.bmc.2016.06.032.
Chengyu Sun 1,  Chen Chen 2,  Shan Xu 3,  Jianqiang Wang 4,  Yan Zhu 5,  Dejia Kong 2,  Hong Tao 2,  Mengjia Jin 2,  Pengwu Zheng 2,  Wufu Zhu 6
Affiliations

Affiliations

  • 1 School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China; Chongqing Three Gorges Medical college, Chongqing, 404120, China.
  • 2 School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China.
  • 3 School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China. Electronic address: Shanxu9891@126.com.
  • 4 Fushun Center for Drug Control, Fushun 113000, China.
  • 5 School of Pharmaceutical Sciences, China Medical University, 92 Beier Road, Shenyang, Liaoning Province 110001, China.
  • 6 School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China. Electronic address: zhuwufu-1122@163.com.
PMID: 27353887 DOI: 10.1016/j.bmc.2016.06.032
Abstract

Herein, we designed and synthesized of a novel series of 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives bearing chromone moiety (10a-j, 13a-j). All the compounds were evaluated for the IC50 values against five Cancer cell lines (A549, PC-3, MCF-7, Hela and HepG2). Seven of the target compounds exhibited moderate to excellent cytotoxicity. For these compounds, we tested their inhibitory activities against mTOR kinase, and four of them were tested their inhibitory activities against PI3Kα kinase in further. The results indicated that the optimized compound 10j showed excellent inhibitory activity and cytotoxicity against mTOR kinase, PI3Kα kinase and five Cancer cell lines with IC50 values of 1.1μM, 0.92μM and 8.77-14.3μM. Structure-activity relationships (SARs) and docking studies indicated that the thiopyrano[4,3-d]pyrimidine scaffolds exerted little effect on antitumor activities of target compounds. Substitutions of chromone moiety at C-6 position with carboxyl were benefit to the antitumor activities.

Keywords

Antitumor activity; Chromone; Docking; PI3Kα; Synthesis; Thiopyranopyrimidine; mTOR.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z