Design, synthesis, in vitro antiproliferative activity properties, quantum chemical and molecular docking studies of novel Schiff bases incorporating pyrimidine nucleus

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Devim M., Akkoç S., Zeyrek C. T., Aslan H. G., Kökbudak Z.

Journal of Molecular Structure, vol.1254, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1254
  • Publication Date: 2022
  • Doi Number: 10.1016/j.molstruc.2022.132421
  • Journal Name: Journal of Molecular Structure
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chimica, Compendex, INSPEC
  • Keywords: Antiproliferative activity, Cancer, DFT calculations, Heterocyclic compound, Molecular docking, Pyrimidine, Schiff base, DERIVATIVES, CRYSTAL
  • Erciyes University Affiliated: Yes


© 2022 Elsevier B.V.In this study, a series of new Schiff bases, based on a pyrimidine core, were synthesized by the condensation reactions of 1-amino-5-(4-methylbenzoyl)-4-p-tolylpyrimidin-2(1H)-one (1a) and 1-amino-5-(4-methylbenzoyl)-4-p-tolylpyrimidine-2(1H)-thione (1b) with different aromatic aldehyde derivatives using p-toluene sulfonic acid as a catalyst at refluxing in ethyl alcohol. The structures of these newly synthesized Schiff bases (2-11) were verified by 1H NMR, 13C NMR, IR, LC-MS (only for 2, 3, 5, 6, 8, 9, 11), and elemental analysis. The presence of characteristic peaks proving the formation of imine supports the molecules' structures. The cytotoxic effects of molecules 2-11 on the viability of breast (MDA-MB-231) and colon (DLD-1) cancer cells were investigated using the MTT method. The molecules (2-11) demonstrated in vitro antiproliferative activity in the MDA-MB-231 cell line with IC50 values ranging from 58.59 µM to ˃200 µM. A compound 3 was particularly found to be the most potent anticancer drug candidate in this series with an IC50 value of 58.59 µM in MDA-MB-231. Unfortunately, neither the activity of this compound nor the others are high enough to be compared with the positive control drug cisplatin against MDA-MB-231 and DLD-1. In addition, Density Functional Theory (DFT) calculations of compounds 3, 4 and 8 were performed and the molecular docking studies of these compounds with breast cancer protein, PDB ID: 1JNX were presented to compare with experimental and theoretical results.