Synthesis and biological evaluation of anthra[1,9-cd]pyrazol-6(2H)-one scaffold derivatives as potential anticancer agents

Several anthrapyrazolone derivatives derived from 7-chloroanthra[1,9-cd]pyrazol-6(2H)-one and 7-chloro-2-(2-hydroxyethyl)anthra[1,9-cd] pyrazol-6(2H)-one have been prepared by the addition or substitution nucleophilic reactions and further transformed into extended tetracyclic systems and fused to different nitrogenheterocyclic rings into the pharmacophore structure moiety. The compounds synthesized were evaluated for their cytotoxic activity and telomerase activity in prostate cancer cell line by SRB assay and in human non-small cell lung carcinoma cell line by TRAP assay, respectively. Compounds 1-6, 13, 14, 16, 17, 19, 21, 23, 28 and 31 were selected by the NCI and only 1, 4, and 16 represent the GI₅₀, TGI and LC₅₀, respectively. Among them, 1 and 16 exhibited distinctive selectivity of GI₅₀ of 10.498μM and 4.542μM over 60 cell lines which is better than the average GI₅₀ (20.3μM) for SP600125 (NSC75890). Overall, the test compounds exhibited different telomerase and cytotoxic activities and only few compounds displayed antitumor activity in the low range.