title: Synthesis and antitumor activity evaluation of 4,6-disubstituted quinazoline derivatives as novel PI3K inhibitors.
abstract: A series of 4,6-disubstituted quinazoline derivatives as potential PI3K inhibitors were designed and synthesized. All compounds exhibited significant anti-proliferative activities against HCT-116 and MCF-7 cell lines, and compounds A7, A9, and A11 displayed the most potent anti-proliferative activity against the HCT-116. Further PI3K inhibitory activity evaluation showed that compound A7 displayed high potency against PI3K enzymes. The in vivo anti-tumor study showed compound A7 can efficaciously inhibit tumor growth in a mice S-180 model. These results suggest that our designed compounds can serve as potent PI3K inhibitors and effective antitumor agents.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Hei
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: xmhcpu@163.com.
authors.forename: Minhang
authors.initials: M
authors.lastname: Xin
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Xie
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Mao
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: sqzhang@xjtu.edu.cn.
authors.forename: San-Qi
authors.initials: SQ
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011799:Quinazolines
keywords: Anti-proliferative; Antitumor; PI3K inhibitor; Quinazoline derivatives; Synthesis