Wydział Chemii

Marcin Stolarczyk

Iwona Bryndal

Agnieszka Matera-Witkiewicz

Tadeusz Lis

Karolina Królewska-Golińska

Marcin Cieślak

Julia Kaźmierczak-Barańska

Jerzy Cieplik

2018

Acta Crystallographica Section C: Structural Chemistry

C74

1138-1145

10.1107/s2053229618012706

Naukowa

Angielski

Artykuł

This article presents the synthesis of three new 4-thio­pyrimidine derivatives obtained from ethyl 4-methyl-2-phenyl-6-sulfanyl­pyrimidine-5-carboxyl­ate as the starting material, namely, ethyl 4-[(4-chloro­benz­yl)sulfan­yl]-6-methyl-2-phenyl­pyrimidine-5-carboxyl­ate, C₂₁H₁₉ClN₂O₂S, (2), {4-[(4-chloro­benz­yl)sulfan­yl]-6-methyl-2-phenyl­pyrimidin-5-yl}methanol, C₁₉H₁₇ClN₂OS, (3), and 4-[(4-chloro­benz­yl)sulfan­yl]-5,6-dimethyl-2-phenyl­pyrimidine, C₁₉H₁₇ClN₂S, (4), which vary in the substituent at the 5-position of the pyrimidine ring. The compounds were characterized by ¹H NMR, ¹³C NMR, IR and mass spectroscopies, and also elemental analysis. The mol­ecular structures were further studied by single-crystal X-ray diffraction. Compound (2) crystallizes in the space group P with one mol­ecule in the asymmetric unit, whereas compounds (3) and (4) crystallize in the space group P2₁/c with two and one mol­ecule, respectively, in their asymmetric units. The conformation of each mol­ecule is best defined by the dihedral angles formed between the pyrimidine ring and the planes of the two aryl substituents attached at the 2- and 4-positions. The only structural difference between the three compounds is the substituent at the 5-position of the pyrimidine ring, but they present significantly different features in the hydrogen-bond inter­actions. Compound (2) displays a one-dimensional chain formed by hydrogen bonds and the chains are further extended into a two-dimensional network. Mol­ecules of (3) and (4) generate one-dimensional chains formed through inter­molecular inter­actions. The study examines the cytotoxicity of compounds (3) and (4) against Human umbilical vein endothelial cells (HUVEC) and HeLa, K562 and CFPAC cancer cell lines. The presence of the hy­droxy­methyl and methyl groups in (3) and (4), respectively, offers an inter­esting new insight into the structures and behaviour of these derivatives. Compound (4) was found to be nontoxic against CFPAC and HUVEC; however, it shows weak activity against the HeLa and K563 cell lines. The presence of a hy­droxy group in (3) significantly increases its cytotoxicity towards both, i.e. the cancer (HeLa, K562 and CFPAC) and normal (HUVEC) cell lines.

4-thio­pyrimidine derivatives, synthesis, crystal structure, cytotoxic activity

http://dx.doi.org/10.1107/s2053229618012706