Synthesis and cytotoxic evaluation of uracil C-Mannich bases

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.

Synthesis and cytotoxic evaluation of uracil C-Mannich bases

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.
Turkish Journal of Chemistry-Cover
  • ISSN: 1300-0527
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Synthesis and structural characterization of novel square pyramidal oxovanadium(IV) complexes with ligands having N and O donor atoms

Ashok Kumar YADAVA, Hardeo Singh YADAV, Uma Shanker YADAV

Three-component Passerini-Smiles coupling reaction of aldehydes and isocyanides with tropolone catalyzed by silica nanoparticles

Abdolhossain MASSOUDI, Issa AMINI, Ali RAMAZANI And

Reduction, Mannich reaction and antimicrobial activity evaluation of some new 1,2,4-triazol-3-one derivatives

Seda FANDAKLI, Serap BAŞOĞLU, Hakan BEKTAŞ, Meltem YOLAL

Determination of ultratrace amounts of dichloro-nitrobenzene and dichloro-nitroaniline in water samples using solidified floating organic drop microextraction (SFODME) and gas chromatography

Shayessteh DADFARNIA, Mohammad MIRZAEI, Ali Mohammad Haji SHABANI

In situ formed 1-hexyl-3-methylimidazolium hexafluorophosphate for dispersive liquid-liquid microextraction of Pd(II) prior to electrothermal AAS and spectrophotometry

Habibollah ESKANDARI

Microwave-assisted synthesis, spectroscopy, and crystal structures of [(H2-(4,4'-bipy)]2+ [Cr2O7]2- and one-dimensional polymeric {[Mn(4,4'-bipy)(Cr2O7)(H2O)2]\}n compounds

Hirihattaya PHETMUNG, Munee WATEH, Chaveng PAKAWATCHAI

Facile and rapid synthesis of some novel polysubstituted imidazoles by employing magnetic $Fe_3O_4$ nanoparticles as a high efficient catalyst

Khalil ESKANDARI, Abdolmohammad GHASEMI, Bahador KARAMI

A new absorption based $CO_2$ sensor based on Schiff base doped ethyl cellulose

Kadriye ERTEKİN, Sevinç Zehra TOPAL, Berrin YENİGÜL, Ayşe ERÇAĞ

Titrimetric determination of anionic surfactant content in anionic/nonionic surfactant mixture solution by anionic surfactant selective electrode

Junwei WANG, Zhiping DU, Wanxu WANG, Wei XUE

A new absorption based CO2 sensor based on Schiff base doped ethyl cellulose

Sevinç Zehra TOPAL, Kadriye ERTEKİIN, Berrin YENİIGÜL, Ayşe ERÇAĞ