Design, synthesis and antiproliferative activity of novel 2,4-diamino-5-methyleneaminopyrimidine derivatives as potential anticancer agents

  • Bioorg Med Chem Lett. 2021 Sep 1:47:128213. doi: 10.1016/j.bmcl.2021.128213.
Qiu Li  1 ,  Lin Chen  1 ,  Xie-Er Jian  1 ,  Dong-Xin Lv  1 ,  Wen-Wei You  1 ,  Pei-Liang Zhao  2
Affiliations
  • 1. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
  • 2. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: [email protected].
PMID: 34157389 DOI: 10.1016/j.bmcl.2021.128213
Abstract

In order to discover new Anticancer agents, 25 novel 2,4-diamino-5-methyleneaminopyrimidine derivatives were designed and synthesized based on our previous work via a ring-opening strategy. Among them, compared with 5-FU, compound 7i exhibited 4.9-, 2.9-, 2.1-, and 3.0-fold improvement in inhibiting HCT116, HT-29, MCF-7, and HeLa cells proliferation with IC50 values of 4.93, 5.57, 8.84, and 14.16 μM, respectively. Moreover, further mechanistic studies indicated that compound 7i could concentration-dependently induce cell cycle arrest and Apoptosis in HCT116 cells. These findings revealed that 2,4-diamino-5-methyleneaminopyrimidine scaffold has potential for further investigation to explore novel Anticancer agents.

Keywords
2,4-Diamino-5-methyleneaminopyrimidines; Antiproliferative activity; Synthesis.