title: Synthesis and anticancer activity of isatin-based pyrazolines and thiazolidines conjugates.
abstract: The synthesis and antitumor activity screening of novel isatin based conjugates with thiazolidine and pyrazoline moieties were performed. Reaction of 3,5-diaryl-4,5-dihydropyrazoles with chloroacetyl chloride yielded starting 2-chloro-1-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-ethanones which were utilized in alkylation of isatin and 5-bromoisatin. Thus, corresponding 1-[2-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-2-oxoethyl]-1H-indole-2,3-diones (1a-1d) have been obtained. The compounds 1a-1d have been used in Knoevenagel condensation with 4-thiazolidinones for obtaining a series of 5-ylidenederivatives 2a-2f and 3a-3d. The synthesized compounds were tested for their anticancer activity in NCI60 cell lines. Among the tested compounds, 5-bromo-1-{2-[5-(4-chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydropyrazol-1-yl]-2-oxoethyl}-1H-indole-2,3-dione (1d) was found to be the most active candidate with selective influence on leukemia subpanel tumor cell lines with GI(50) values range of 0.69-3.35 µM.
authors.affiliation: Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Ukraine, Lviv, Ukraine.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Havrylyuk
authors.forename: Natalya
authors.initials: N
authors.lastname: Kovach
authors.forename: Borys
authors.initials: B
authors.lastname: Zimenkovsky
authors.forename: Olexandr
authors.initials: O
authors.lastname: Vasylenko
authors.forename: Roman
authors.initials: R
authors.lastname: Lesyk
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007510:Isatin / Q000031:analogs & derivatives* / Q000737:chemistry; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism; D053778:Thiazolidines / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles; D053778:Thiazolidines; D007510:Isatin