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

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.

• Authors: Mohammad Abdel-Halim, 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
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 21 Issue 23 Pg. 7343-56 (Dec 01 2013) ISSN: 1464-3391 [Electronic] England
• PMID: 24139845 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Growth Inhibitors
• Tumor Suppressor Protein p53

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Cell Line, Tumor
• Gene Deletion
• Gene Expression Regulation, Neoplastic
• Growth Inhibitors (chemistry, pharmacology)
• Humans
• Neoplasms (drug therapy, genetics)
• Structure-Activity Relationship
• Tumor Suppressor Protein p53 (genetics)