Synthesis and cytotoxic evaluation of uracil C-Mannich bases

Hüseyin Istanbullu, István Zupkó, Vildan Alptüzün, Erçin Erciyas

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Abstract

This study covers the design, synthesis, characterization, and cytotoxic activity of a series of uracil C-Mannich bases. Among them, one hybrid compound (1), a molecular combination of the potential antimetabolite substituted uracil and nitrogen mustard, having potential alkylating capability, was prepared as a Mannich base. The other compound was synthesized with the replacement of chlorines in the ethyl chains with hydroxyl groups for testing for anticancer activity. Some of Mannich bases having several amino groups with different pKa values were also synthesized and investigated in terms of cytotoxic activity. Their chemical structures were confirmed by means of their UV, IR, 1H-NMR, 13C-NMR, and MS data. Compounds 6 with diethylamine and 8 with piperazine are reported for the first time in the literature and compounds 1, 4, and 5 containing nitrogen mustard, pyrolidine, and diethanolamine, respectively, as amine function are reported for first time with detailed spectral data herein. Morpholine, piperidine, and dimethylamine were used in Mannich reactions for the synthesis of compounds 2, 3 and 7. We assessed their biological activities using MTT assays on 3 human cell lines: HeLa (cervix adenocarcinoma), MCF7 (breast adenocarcinoma), and A431 (skin epidermoid carcinoma). While compounds 2-8 have the potential to deaminate, forming ortho-quinone methides, which would be capable of alkylating cellular thiols, compound 1 has the potential to give aziridinium ion for nucleophilic alkylation. Our results are discussed in terms of the significance of these compounds in pharmaceutical use.

Original languageEnglish
Pages (from-to)583-592
Number of pages10
JournalTurkish Journal of Chemistry
Volume36
Issue number4
DOIs
Publication statusPublished - Jul 23 2012

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Keywords

  • Anti-cancer compounds
  • Antiproliferative effect
  • Mannich base
  • Uracil

ASJC Scopus subject areas

  • Chemistry(all)

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