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Synthesis and anticancer activity of thiosubstituted purines.

Kowalska A, Latocha M, Pluta K - Med Chem Res (2015)

Bottom Line: The azathioprine analogs (2a, 2b, and 3a) were more active than azathioprine against SBN-19 and C-32 cell lines.The sulfenamide and sulfonamide derivatives of purine were very weak active against tested cell lines.All studied thiopurines were less toxic than cisplatin.

View Article: PubMed Central - PubMed

Affiliation: Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland.

ABSTRACT

New thiopurines with the propargylthio, pyrrolidinobutynylthio, sulfenamide, and sulfonamide groups in the pyrimidine ring were synthesized. The anticancer activity of these compounds and previously obtained 2- or 6-substituted azathioprine analogs and dialkylaminoalkylthiopurines were tested in vitro against three cell lines: glioblastoma SNB-19, melanoma C-32, and human ductal breast epithelial tumor T47D. 2-Chloro-7-methyl-6-pyrrolidinobutynylthiopurine (5b) was the most potent compound against SBN-19 and C-32 cell lines with the activity similar to cisplatin (EC50 = 5.00 and 7.58 μg/ml, respectively). The dialkylaminoalkylthio derivatives (4b, 4c, 4e, and 4f) showed good activity against SBN-19 cell line (EC50 < 10 μg/ml). The azathioprine analogs (2a, 2b, and 3a) were more active than azathioprine against SBN-19 and C-32 cell lines. The sulfenamide and sulfonamide derivatives of purine were very weak active against tested cell lines. All studied thiopurines were less toxic than cisplatin.

No MeSH data available.


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Synthesis of 2- or 6-substituted azathioprine analogs 2, 3, dialkylaminoalkylthiopurines 4, propargylthio- and pyrrolidinobutynylthiopurines 5
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Sch1: Synthesis of 2- or 6-substituted azathioprine analogs 2, 3, dialkylaminoalkylthiopurines 4, propargylthio- and pyrrolidinobutynylthiopurines 5

Mentions: All thiosubstituted 7-methylpurines were obtained from 2-substituted 7-methylpurine-6-thiones 1a–c and 7-methylpurine-2,6-dithiones 1d. Purinyl sulfides 2–4 with the pharmacophoric 1-methyl-4-nitroimidazol-5-yl and dialkylaminoalkyl groups in positions 2 and 6 were obtained according to the procedures published previously (Kowalska and Pluta, 2008; Kowalska et al., 2009; Kowalska and Pluta, 2012). The alkynylthio derivatives 5 were obtained from 2-chloro derivative 1a and propargyl bromide and further via Mannich reaction with pyrrolidine (Scheme 1).Scheme 1


Synthesis and anticancer activity of thiosubstituted purines.

Kowalska A, Latocha M, Pluta K - Med Chem Res (2015)

Synthesis of 2- or 6-substituted azathioprine analogs 2, 3, dialkylaminoalkylthiopurines 4, propargylthio- and pyrrolidinobutynylthiopurines 5
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4491105&req=5

Sch1: Synthesis of 2- or 6-substituted azathioprine analogs 2, 3, dialkylaminoalkylthiopurines 4, propargylthio- and pyrrolidinobutynylthiopurines 5
Mentions: All thiosubstituted 7-methylpurines were obtained from 2-substituted 7-methylpurine-6-thiones 1a–c and 7-methylpurine-2,6-dithiones 1d. Purinyl sulfides 2–4 with the pharmacophoric 1-methyl-4-nitroimidazol-5-yl and dialkylaminoalkyl groups in positions 2 and 6 were obtained according to the procedures published previously (Kowalska and Pluta, 2008; Kowalska et al., 2009; Kowalska and Pluta, 2012). The alkynylthio derivatives 5 were obtained from 2-chloro derivative 1a and propargyl bromide and further via Mannich reaction with pyrrolidine (Scheme 1).Scheme 1

Bottom Line: The azathioprine analogs (2a, 2b, and 3a) were more active than azathioprine against SBN-19 and C-32 cell lines.The sulfenamide and sulfonamide derivatives of purine were very weak active against tested cell lines.All studied thiopurines were less toxic than cisplatin.

View Article: PubMed Central - PubMed

Affiliation: Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland.

ABSTRACT

New thiopurines with the propargylthio, pyrrolidinobutynylthio, sulfenamide, and sulfonamide groups in the pyrimidine ring were synthesized. The anticancer activity of these compounds and previously obtained 2- or 6-substituted azathioprine analogs and dialkylaminoalkylthiopurines were tested in vitro against three cell lines: glioblastoma SNB-19, melanoma C-32, and human ductal breast epithelial tumor T47D. 2-Chloro-7-methyl-6-pyrrolidinobutynylthiopurine (5b) was the most potent compound against SBN-19 and C-32 cell lines with the activity similar to cisplatin (EC50 = 5.00 and 7.58 μg/ml, respectively). The dialkylaminoalkylthio derivatives (4b, 4c, 4e, and 4f) showed good activity against SBN-19 cell line (EC50 < 10 μg/ml). The azathioprine analogs (2a, 2b, and 3a) were more active than azathioprine against SBN-19 and C-32 cell lines. The sulfenamide and sulfonamide derivatives of purine were very weak active against tested cell lines. All studied thiopurines were less toxic than cisplatin.

No MeSH data available.


Related in: MedlinePlus