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

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 μM). 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 μM), 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 μM, 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.

A series of 3-(4-chlorophenyl)-[1,2-c]pyrazol(in)es-substituted with benzenesulfonamides, N1,N3-disubstituted sulfonylurea and sulfonylthiourea pharmacophores, and some derived thiazolidinone and thiazoline ring systems and evaluated for their antitumor activity according to the protocol of the NCI. Eight compounds showed promising broad spectrum antitumor activity against most of the tested subpanel tumor cell lines.Figure optionsDownload as PowerPoint slide