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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.


Related in: MedlinePlus

2D NMR experiments for compound 5a
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Sch3: 2D NMR experiments for compound 5a

Mentions: The structure of all new compounds was determined by the spectral data analysis: 1H and 13C NMR, EI, CI or FAB MS, and HR MS. 1H NMR spectra of new compounds revealed H-8, NCH3 proton signals, and protons from C-2 (OCH3, SCH3) and C-6 (CH2C6H5, NH2, N(C2H5)2, NHC6H5, SCH2CCH, SCH2CCCH2NC4H8, SNH2, SO2NH2) substituents. 13C NMR spectra showed primary, secondary, tertiary, and quaternary carbon signals. In order to assign all of these signals, 2D NMR techniques (HSQC—the primary, secondary, and tertiary carbon atoms connected with the hydrogen atoms and HMBC—the primary, tertiary, and quaternary carbon atoms connected with the hydrogen atoms via two and mainly three bonds) for selected compounds (5a, 10e) were used. For compounds 5a, in the HSQC spectrum the H-8 proton at 8.59 ppm correlated with the signal at 151.09 ppm (C-8), the SCH2 proton at 4.22 ppm correlated with the signal at 18.09 ppm (C, SCH2), and the proton at 4.04 ppm (NCH3) correlated with the signal at 34.84 ppm (C, NCH3). The HMBC spectrum revealed correlation via three bonds between the H-8 proton at 8.59 ppm and the carbon signals at 34.84 ppm (C, NCH3), at 123.16 ppm (C-5), and at 160.52 ppm (C-4). The proton signal at 4.22 ppm (H, SCH2) correlated with the signals of carbon atoms via two bonds at 79.55 ppm (C, CCH) and via three bonds at 74.67 ppm (C, CH) and at 153.99 ppm (C-6). The proton signal at 4.04 ppm (H, NCH3) correlated via three bonds with the signals at 123.16 ppm (C-5) and at 151.09 ppm (C-8). The proton–carbon correlation was presented in Scheme 3.Scheme 3


Synthesis and anticancer activity of thiosubstituted purines.

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

2D NMR experiments for compound 5a
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Sch3: 2D NMR experiments for compound 5a
Mentions: The structure of all new compounds was determined by the spectral data analysis: 1H and 13C NMR, EI, CI or FAB MS, and HR MS. 1H NMR spectra of new compounds revealed H-8, NCH3 proton signals, and protons from C-2 (OCH3, SCH3) and C-6 (CH2C6H5, NH2, N(C2H5)2, NHC6H5, SCH2CCH, SCH2CCCH2NC4H8, SNH2, SO2NH2) substituents. 13C NMR spectra showed primary, secondary, tertiary, and quaternary carbon signals. In order to assign all of these signals, 2D NMR techniques (HSQC—the primary, secondary, and tertiary carbon atoms connected with the hydrogen atoms and HMBC—the primary, tertiary, and quaternary carbon atoms connected with the hydrogen atoms via two and mainly three bonds) for selected compounds (5a, 10e) were used. For compounds 5a, in the HSQC spectrum the H-8 proton at 8.59 ppm correlated with the signal at 151.09 ppm (C-8), the SCH2 proton at 4.22 ppm correlated with the signal at 18.09 ppm (C, SCH2), and the proton at 4.04 ppm (NCH3) correlated with the signal at 34.84 ppm (C, NCH3). The HMBC spectrum revealed correlation via three bonds between the H-8 proton at 8.59 ppm and the carbon signals at 34.84 ppm (C, NCH3), at 123.16 ppm (C-5), and at 160.52 ppm (C-4). The proton signal at 4.22 ppm (H, SCH2) correlated with the signals of carbon atoms via two bonds at 79.55 ppm (C, CCH) and via three bonds at 74.67 ppm (C, CH) and at 153.99 ppm (C-6). The proton signal at 4.04 ppm (H, NCH3) correlated via three bonds with the signals at 123.16 ppm (C-5) and at 151.09 ppm (C-8). The proton–carbon correlation was presented in Scheme 3.Scheme 3

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