title: Polysubstituted pyrazoles, part 6. Synthesis of some 1-(4-chlorophenyl)-4-hydroxy-1H-pyrazol-3-carbonyl derivatives linked to nitrogenous heterocyclic ring systems as potential antitumor agents.
abstract: The synthesis of two novel series of 1-(4-chlorophenyl)-4-hydroxy-1H-pyrazoles linked to either polysubstituted 1H-pyrazole counterparts through a carbonyl bridge, or to some biologically-active nitrogenous heterocycles by an amide linker, is described. Ten of the newly synthesized compounds were selected by the National Cancer Institute (NCI) in vitro disease-oriented antitumor screening to be evaluated for their antitumor activity. The most active six compounds 2, 3, 6, 7, 13 and 14 revealed a significant broad spectrum of antitumor potential against most of the tested subpanel tumor cell lines at the GI(50) and TGI levels, together with a mild cytotoxic (LC(50)) activity. The pyrazolinedione analog 7 displayed remarkable growth inhibition and cytostatic effects (GI(50) and TGI MG-MID values 0.67 and 53.8microM, respectively). Compounds 13 (GI(50), TGI, and LC(50) MG-MID values 0.08, 30.9 and 93.3microM) and 14 (GI(50), TGI, and LC(50) MG-MID values 0.36, 8.78 and 69.3microM, respectively) proved to be the most active antitumor members identified in this study.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdul-Aziz University, PO Box 80260, Jeddah 21589, Saudi Arabia. sherifrostom@yahoo.com
authors.forename: Sherif A F
authors.initials: SA
authors.lastname: Rostom
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D007364:Intercalating Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles