title: Design, synthesis and antiproliferative activity of novel 5-nitropyrimidine-2,4-diamine derivatives bearing alkyl acetate moiety.
abstract: In order to discover new anticancer drug leads, a series of novel alkylamino pyrimidine derivatives were designed and synthesized based on our previous work via a ring-opening strategy. Biological evaluation with four human cancer cell lines (MDA-MB-231, A549, HepG2, and MCF-7) showed that most of these compounds possessed moderate to potent antiproliferative activities. The most promising compound 7w displayed a three-fold improvement compared with commercial anticancer drug fluorouracil in inhibiting HepG2 cell proliferation with IC50 value of 10.37 μM. Moreover, flow-activated cell sorting analysis suggested that compound 7w mainly arrested HepG2 cells in G2/M stage. Hence, it could serve as a promising lead for the design of novel anticancer small-molecule drugs.
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: plzhao@smu.edu.cn.
authors.forename: Pei-Liang
authors.initials: PL
authors.lastname: Zhao
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Hai-Kui
authors.initials: HK
authors.lastname: Yang
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: youww@smu.edu.cn.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: You
mesh_terms: D000085:Acetates / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000085:Acetates; D000970:Antineoplastic Agents; D011743:Pyrimidines
keywords: 2,4-Diaminopyrimidines; Alkylamino pyrimidines; Antiproliferative activity; Synthesis