Synthesis and biological evaluation of novel indole-pyrimidine hybrids bearing morpholine and thiomorpholine moieties

Peng Cheng Diao, Qiu Li, Meng Jin Hu, Yu Feng Ma, Wen Wei You, Kwon Ho Hong, Pei Liang Zhao

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Based on our previous screening hit compound 1, a series of novel indole-pyrimidine hybrids possessing morpholine or thiomorpholine moiety were synthesized via an efficient one-pot multistep synthetic method. The antiproliferative activities of the synthesized compounds were evaluated in vitro against four cancer cell lines including HeLa, MDA-MB-231, MCF-7, and HCT116. The results revealed that most compounds possessed moderate to excellent potency. The IC50 values of the most promising compound 15 are 0.29, 4.04, and 9.48 μM against MCF-7, HeLa, and HCT116 cell lines, respectively, which are 48.0, 4.9, and 1.8 folds more active than the lead compound 1. Moreover, fluorescence-activated cell sorting analysis revealed that compound 14 showing the highest activity against HeLa (IC50 = 2.51 μM) displayed a significant effect on G2/M cell-cycle arrest in a concentration-dependent manner in HeLa cell line. In addition, representative nine active hybrids were evaluated for tubulin polymerization inhibitory activities, and compound 15 exhibited the most potent anti-tubulin activity showing 42% inhibition at 10 μM. These preliminary results encourage a further investigation on indole-pyrimidine hybrids for the development of potent anticancer agents that inhibit tubulin polymerization.

Original languageEnglish (US)
Pages (from-to)110-118
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
StatePublished - 2017

Bibliographical note

Funding Information:
We should thank Dr. Hong-Bing Zhao (Shanghai TANG Bioscience Co., Ltd.) for the test of tubulin polymerisation activity. The present work was supported by National Natural Science Foundation of China (21372113 and 21102069), and the Special Funds for the Cultivation of Guangdong College Students’ Scientific and Technological Innovation. (“Climbing Program” Special Funds.) (No. pdjh2016b0108).

Publisher Copyright:
© 2017 Elsevier Masson SAS


  • Antiproliferative activity
  • Indole-pyrimidine
  • Morpholine
  • Thiomorpholine
  • Tubulin polymerization


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