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, cilt.152, sa.5, ss.513-522, 2021 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 152 Sayı: 5
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1007/s00706-021-02761-3
  • Dergi Adı: MONATSHEFTE FUR CHEMIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core
  • Sayfa Sayıları: ss.513-522
  • Van Yüzüncü Yıl Üniversitesi Adresli: Evet

Özet

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.