title: Synthesis and anticancer activity of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives bearing chromone moiety.
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.
authors.affiliation: School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China; Chongqing Three Gorges Medical college, Chongqing, 404120, China.
authors.forename: Chengyu
authors.initials: C
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China. Electronic address: Shanxu9891@126.com.
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Fushun Center for Drug Control, Fushun 113000, China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, China Medical University, 92 Beier Road, Shenyang, Liaoning Province 110001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China.
authors.forename: Dejia
authors.initials: D
authors.lastname: Kong
authors.affiliation: School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Tao
authors.affiliation: School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China.
authors.forename: Mengjia
authors.initials: M
authors.lastname: Jin
authors.affiliation: School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China.
authors.forename: Pengwu
authors.initials: P
authors.lastname: Zheng
authors.affiliation: School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China. Electronic address: zhuwufu-1122@163.com.
authors.forename: Wufu
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002867:Chromones / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D066244:Proton Magnetic Resonance Spectroscopy; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000970:Antineoplastic Agents; D002867:Chromones; D011743:Pyrimidines
keywords: Antitumor activity; Chromone; Docking; PI3Kα; Synthesis; Thiopyranopyrimidine; mTOR