Trisubstituted and tetrasubstituted pyrazolines as a novel class of cell-growth inhibitors in tumor cells with wild type p53

  • Bioorg Med Chem. 2013 Dec 1;21(23):7343-56. doi: 10.1016/j.bmc.2013.09.055.
Mohammad Abdel-Halim  1 ,  Adam B Keeton ,  Evrim Gurpinar ,  Bernard D Gary ,  Simon M Vogel ,  Matthias Engel ,  Gary A Piazza ,  Frank M Boeckler ,  Rolf W Hartmann ,  Ashraf H Abadi
Affiliations
  • 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt; Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2.3, D-66123 Saarbrücken, Germany.
PMID: 24139845 DOI: 10.1016/j.bmc.2013.09.055
Abstract

Derivatives with scaffolds of 1,3,5-tri-substituted pyrazoline and 1,3,4,5-tetra-substituted pyrazoline were synthesized and tested for their inhibitory effects versus the p53(+/+) HCT116 and p53(-/-) H1299 human tumor cell lines. Several compounds were active against the two cell lines displaying IC50 values in the low micromolar range with a clearly more pronounced effect on the p53(+/+) HCT116 cells. The compound class shows excellent developability due to the modular synthesis, allowing independent optimization of all three to four key substituents to improve the properties of the molecules.

Keywords
Anticancer; Pyrazoline; p53.