title: 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.affiliation: 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.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdel-Halim
authors.forename: Adam B
authors.initials: AB
authors.lastname: Keeton
authors.forename: Evrim
authors.initials: E
authors.lastname: Gurpinar
authors.forename: Bernard D
authors.initials: BD
authors.lastname: Gary
authors.forename: Simon M
authors.initials: SM
authors.lastname: Vogel
authors.forename: Matthias
authors.initials: M
authors.lastname: Engel
authors.forename: Gary A
authors.initials: GA
authors.lastname: Piazza
authors.forename: Frank M
authors.initials: FM
authors.lastname: Boeckler
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
authors.forename: Ashraf H
authors.initials: AH
authors.lastname: Abadi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006131:Growth Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D016159:Tumor Suppressor Protein p53
keywords: Anticancer; Pyrazoline; p53