Synthesis of Isomeric Analogs of Azathioprine

Kowalska, Alicja; Pluta, Krystian; Suwińska, Kinga

doi:10.3987/com-09-11742

Cited by 5 publications

(7 citation statements)

References 26 publications

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“…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 ).…”

Section: Resultsmentioning

confidence: 99%

“…Our previous research demonstrated the effective synthesis of thiosubstituted purines such as 2- or 6-substituted azathioprine analogs (Kowalska and Pluta, 2008 ; Kowalska et al ., 2009 ) and dialkylaminoalkylthiopurines (Kowalska and Pluta, 2012 ). The aim of this study was to elaborate synthesis of new thiopurines with the propargylthio, pyrrolidinobutynylthio, sulfenamide, and sulfonamide groups in the pyrimidine ring, to examine anticancer activity of not only those compounds but also previously synthesized thiopurines and to discuss the structure–activity relationship.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and anticancer activity of thiosubstituted purines

2015

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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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00044-015-1364-2) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and anticancer activity of thiosubstituted purines

2015

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“…In contrast to compounds P 1 -P 18 , compound P 19 possesses exceptional conformation where two 1-methyl-4-nitroimidazolylthio moieties were almost parallel showing the donor-acceptor interactions between them in the X-ray analysis. [11] The RP TLC method has been successfully used for estimation of the parameter log P as log P TLC values from R M0 values using calibration …”

Section: Resultsmentioning

confidence: 99%

“…[11] The 6-imidazol-5-ylthio-2-purinone P 15 and 2-purinethione P 16 were synthetized from 7-methyl-6-thioxanthine and from 2-benzylthio-7methyl-6-purinethione with 5-chloro-1-methyl-4-nitroimidazole in ethanol, respectively. [10] Materials Azathioprine (AZA) was obtained from Sigma.…”

Section: Methodsmentioning

confidence: 99%

“…In continuation of our studies on purine derivatives, recently, we described the effective synthesis of 2-or 6-substituted azathioprine analogs. [10,11] The role of compound lipophilicity in biological activity and related interactions has been well established, particularly over the last 30 years. Lipophilicity is considered one of the most important physicochemical properties in the design process of a new bioactive substance.…”

Section: Introductionmentioning

confidence: 99%

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Rp TLC Assay of the Lipophilicity of New Azathioprine Analogs

Kowalska

Pluta

2012

Journal of Liquid Chromatography & Related Technologies

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& The lipophilicity parameters of azathioprine (P 20 ) and nineteen of its derivatives (P 1 -P 19 ) were determined experimentally (R M0 and log P TLC ) by reversed-phase thin-layer chromatography and were compared with theoretical values (log P calcd ) obtained using 9 computational methods. The parameter R M0 and specific hydrophobic surface area b were significantly intercorrelated showing a congeneric class of the azathioprine derivatives. The parameter R M0 was correlated with molecular descriptors (molar mass, molar volume, and molar refractivity) and was converted into the parameter log P TLC by use of a calibration curve obtained for five standards. The theoretical parameter log P calcd differed dramatically depending on the calculating programs. The log P calcd values were compared with experimental log P TLC values showing low prediction power of calculated programs for compounds P 1 -P 20 . All compounds P 1 -P 19 were more lipophilic than azathioprine. The determined parameters were discussed in the terms of the structure-lipophilicity relationships.

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