Synthesis and anticancer activity of novel nonfused bicyclic thiazolidinone derivatives

Dmytro Havrylyuk, Borys Zimenkovsky, Roman Lesyk

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

A series of new 2-{4-oxo-2-[(4-oxothiazolidin-2-ylidene)-hydrazono]- thiazolidin-5-yl}-N-arylacetamides (4a-e), 5-(2-oxo-2-aryl-ethyl)-2-[(4- oxothiazolidin-2-ylidene)-hydrazono]-thiazolidine-4-ones (5a-d), 2-(4-oxo-2-[(2-oxothiazolidin-4-ylidene)-hydrazono]-thiazolidin-5-yl) -N-arylacetamides (7a-e), and 5-(2-oxo-2-aryl-ethyl)-2-[(2-oxothiazolidin-4- ylidene)-hydrazono]-thiazolidine-4-ones (8a-d) have been synthesized starting from 2-thioxothiazolidin-4-one and 4-thioxothiazolidin-2-one through a multistep reaction sequence. 2-Thioxothiazolidin-4-one was alkylated via the intermediate formation of the triethylammonium salt 1 by ethyl chloroacetate. Compound 2 and 4-thioxothiazolidin-2-one reacted with thiosemicarbazides to give the 1-(4-thiazolidinone-2-ylidene)-4-R-thiosemicarbazones (3a,b) and 1-(2-thiazolidinone-4-ylidene)thiosemicarbazones (6a,b), respectively. Following [2+3]-cyclization of thiazolidinone-substituted thiosemicarbazones (3a,b and 6a,b) with N-arylmaleimides and aroylacrylic acids as equivalents of dielectrophilic synthon [C2]2 +, novel non-fused bicyclic thiazolidinones (4a-e, 5a-d, 7a-e, 8a-d) were synthesized. The structures of the new compounds (4a-e, 5a-d, 7a-e, 8a-d) were established on the basis of their elemental analysis and 1H NMR and mass spectral data. Eight of the synthesized compounds were tested, and three of them displayed different levels of antitumor activity. The most efficient antitumor agent2-{4-oxo-3-furylmethyl-2-[(4-oxothiazolidin-2-ylidene)- hydrazono]-thiazolidin-5-yl}-N-4-chlorophenylacetamide (4d) was found to be active against leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancer cell lines with mean lgGI50 and lgTGI values of -5.35 and -4.78, respectively.

Original languageEnglish
Pages (from-to)638-650
Number of pages13
JournalPhosphorus, Sulfur and Silicon and the Related Elements
Volume184
Issue number3
DOIs
StatePublished - Mar 2009

Keywords

  • Anticancer activity
  • Thiazolidinones
  • [2+3]-cyclization

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Inorganic Chemistry

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