Synthesis and cytotoxic evaluation of uracil C-Mannich bases

Hüseyin İSTANBULLU; István ZUPKÓ

Article Details

Synthesis and cytotoxic evaluation of uracil C-Mannich bases

Authors:

Hüseyin İSTANBULLU | István ZUPKÓ

Publisher:

TUBITAK

Journal:

Turkish Journal of Chemistry 2012 Vol.36 Issue 4, pp.583-592

Document Type:

Article

Publication Date:

3/2012

Document Language:

Turkish

Document ID (Org No.):

2000727591

Frequency:

Bimonthly

eISSN:

1303-6130

pISSN:

1300-0527

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.

 

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.

Article Details

Synthesis and cytotoxic evaluation of uracil C-Mannich bases

Authors: Hüseyin İSTANBULLU | István ZUPKÓ

Publisher: TUBITAK

Journal: Turkish Journal of Chemistry 2012 Vol.36 Issue 4, pp.583-592

Document Type: Article

Publication Date: 3/2012

Document Language: Turkish

Document ID (Org No.): 2000727591

Frequency: Bimonthly

eISSN: 1303-6130

pISSN: 1300-0527

Issues

Authors:

Hüseyin İSTANBULLU | István ZUPKÓ

Publisher:

TUBITAK

Journal:

Turkish Journal of Chemistry 2012 Vol.36 Issue 4, pp.583-592

Document Type:

Article

Publication Date:

3/2012

Document Language:

Turkish

Document ID (Org No.):

2000727591

Frequency:

Bimonthly

eISSN:

1303-6130

pISSN:

1300-0527