Title:Synthesis, Characterization, Antitumor Potential, BSA and DNA Binding
Properties, and Molecular Docking Study of Some Novel 3-Hydroxy-3-
Pyrrolin-2-Ones
Volume: 18
Issue: 3
Author(s): Nenad Joksimović*, Jelena Petronijević, Emilija Milović, Nenad Janković, Dejan Baskić, Suzana Popović, Danijela Todorović, Sanja Matić, Milan Vraneš and Aleksandar Tot
Affiliation:
- Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, Kragujevac 34000,
Serbia
- Department of Sciences, Institute for Information Technologies Kragujevac, University of Kragujevac, Jovana
Cvijića bb, Kragujevac 34000, Serbia
Keywords:
3-hydroxy-3-pyrrolin-2-ones, biological evaluation, mechanisms of cytotoxic activity, DNA binding study, BSAbinding study, molecular docking study.
Abstract:
Background: In order to make progress in discovering the new agents for cancer treatment
with improved properties and considering the fact that 3-hydroxy-3-pyrrolin-2-ones belong to a
class of biologically active compounds, we tested series of eleven novels 1,5-diaryl-4-(2-
thienylcarbonyl)-3-hydroxy-3-pyrrolin-2-ones for their antitumor potential.
Methods: All novel compounds were characterized by spectral (IR, NMR, MS) and elemental analysis.
All novel 3-hydroxy-3-pyrrolin-2-ones were screened for their cytotoxic activity on two cancer
cell lines, SW480 and MDA-MB 231, and non-transformed fibroblasts (MRC-5).
Results: Compounds B8, B9, and B10 showed high cytotoxicity on SW480 cells together with good
selectivity towards MRC-5 cells. It is important to empathize that the degree of selectivity of B8 and
B10 was high (SI = 5.54 and 12.09, respectively). Besides, we explored the mechanisms of cytotoxicity
of novel derivatives, B8, B9, and B10. The assay showed that tested derivatives induce an apoptotic
type of cell death in SW480 cells, with a minor percent of necrotic cells. Additionally, to better
understand the suitability of the compounds for potential use as anticancer medicaments, we studied
their interactions with biomacromolecules (DNA or BSA). The results indicated that the tested compounds
have a great affinity to displace EB from the EB-DNA complex through intercalation. Also,
DNA and BSA molecular docking study was performed to predict the binding mode and the interaction
region of the compounds.
Conclusion: Achieved results indicate that our compounds have the potential to become candidates
for use as medicaments.
