Synthesis of novel 1,3-disubstituted pyrrolo[1,2-a]pyrazine derivatives and antiproliferative effects on glioblastoma cell line

Tan Uygun M.

MONATSHEFTE FUR CHEMIE, vol.152, no.5, pp.513-522, 2021 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 152 Issue: 5
  • Publication Date: 2021
  • Doi Number: 10.1007/s00706-021-02761-3
  • Journal Name: MONATSHEFTE FUR CHEMIE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core
  • Page Numbers: pp.513-522
  • Van Yüzüncü Yıl University Affiliated: Yes

Abstract

Novel pyrrolopyrazine derivatives were synthesized according to a very simple protocol starting from N-propargylated-2-acyl-pyrroles. These derivatives were obtained in good to excellent yields (68-94%) in the presence of ammonium acetate and Cs2CO3, and then subjected to cytotoxicity testing against glioblastoma cell line T98G. Among the tested molecules, those that cause 68.9%, 59.1%, and 37.5% cell death, were identified as lead compounds. The structure-activity relationship (SAR) study revealed that conformation, pi-pi interactions, and halogen bonds could be important for efficiency. Finally, theoretical ADMET studies on pyrrolopyrazine derivatives demonstrated that pharmacokinetic phases are suitable.