title: Synthesis and in vitro antitumor evaluation of some indeno[1,2-c]pyrazol(in)es substituted with sulfonamide, sulfonylurea(-thiourea) pharmacophores, and some derived thiazole ring systems.
abstract: The synthesis of a series of 3-(4-chlorophenyl)-[1,2-c]pyrazol(in)es substituted with benzenesulfonamide, N1,N3-disubstituted sulfonylurea, sulfonylthiourea pharmacophores, and some derived thiazolidinone and thiazoline ring systems is described. All the newly synthesized target compounds were subjected to the NCI-in vitro disease-oriented antitumor screening to be evaluated for their antitumor activity. Eight compounds namely; 2-4, 7, 8, 10, 13, and 16; showed promising broad spectrum antitumor activity against most of the tested subpanel tumor cell lines (GI50 < 100 microM). Compound 3, 4-(3-(4-chlorophenyl)-4H-indeno[1,2-c]pyrazol- 2-yl)-benzenesulfonamide; although it did not show the highest growth inhibitory value (GI50 (MG-MID) 13.2 microM), it proved to be the most active analog in this study with the highest cytostatic and cytotoxic potentials (TGI and LC50 (MG-MID) concentrations of 33.1 and 66.1 microM, respectively). In general, the oxidized pyrazoles displayed better antitumor activity than their parent pyrazoline analogs, whereas the benzenesulfonamides and the N1, N3-disubstituted sulfonylureas showed significant better antitumor spectrum than the sulfonylthioureido and the derived thiazole analogs.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Medicine, King Abdulaziz University, PO Box 80205, 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; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007192:Indenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D013453:Sulfonylurea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007192:Indenes; D007202:Indicators and Reagents; D011720:Pyrazoles; D013449:Sulfonamides; D013453:Sulfonylurea Compounds; D013844:Thiazoles