Synthesis, Crystal Structure, and Biological Evaluation of Novel 5-Hydroxymethylpyrimidines

Pyrimidine displays a wide array of bioactivities, and thence, it is still considered a potent unit of new drug research. Its derivative, 5-hydroxymethylpyrimidine, can be found as a scaffold of nontypical nitrogen bases in DNA and as a core of some natural bioactive compounds. In this study, we obt...

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Autores principales: Marcin Stolarczyk, Agnieszka Matera-Witkiewicz, Aleksandra Wolska, Magdalena Krupińska, Aleksandra Mikołajczyk, Anna Pyra, Iwona Bryndal
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Lenguaje:EN
Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:68f751a1eae340b89839a40e4edb3d002021-11-25T18:14:42ZSynthesis, Crystal Structure, and Biological Evaluation of Novel 5-Hydroxymethylpyrimidines10.3390/ma142269161996-1944https://doaj.org/article/68f751a1eae340b89839a40e4edb3d002021-11-01T00:00:00Zhttps://www.mdpi.com/1996-1944/14/22/6916https://doaj.org/toc/1996-1944Pyrimidine displays a wide array of bioactivities, and thence, it is still considered a potent unit of new drug research. Its derivative, 5-hydroxymethylpyrimidine, can be found as a scaffold of nontypical nitrogen bases in DNA and as a core of some natural bioactive compounds. In this study, we obtained a series of 5-hydroxymethylpyrimidines that vary in the 4-position by the reduction of proper esters. All compounds were characterized by spectroscopic analysis, and single-crystal X-ray diffraction was performed for some of them. Biological investigations estimated cytotoxic properties against normal (RPTEC) and cancer (HeLa, HepaRG, Caco-2, AGS, A172) cell lines. It was found that the derivatives with an aliphatic amino group at the 4-position are generally less toxic to normal cells than those with a benzylsulfanyl group. Moreover, compounds with bulky constituents exhibit better anticancer properties, though at a moderate level. The specific compounds were chosen due to their most promising IC50 concentration for in silico study. Furthermore, antimicrobial activity tests were performed against six strains of bacteria and one fungus. They demonstrated that only derivatives with at least three carbon chain amino groups at the 4-position have weak antibacterial properties, and only the derivative with 4-benzylsulfanyl constituent exhibits any antifungal action.Marcin StolarczykAgnieszka Matera-WitkiewiczAleksandra WolskaMagdalena KrupińskaAleksandra MikołajczykAnna PyraIwona BryndalMDPI AGarticlepyrimidinesanticancer activitysingle-crystal X-ray diffractionTechnologyTElectrical engineering. Electronics. Nuclear engineeringTK1-9971Engineering (General). Civil engineering (General)TA1-2040MicroscopyQH201-278.5Descriptive and experimental mechanicsQC120-168.85ENMaterials, Vol 14, Iss 6916, p 6916 (2021)
institution DOAJ
collection DOAJ
language EN
topic pyrimidines
anticancer activity
single-crystal X-ray diffraction
Technology
T
Electrical engineering. Electronics. Nuclear engineering
TK1-9971
Engineering (General). Civil engineering (General)
TA1-2040
Microscopy
QH201-278.5
Descriptive and experimental mechanics
QC120-168.85
spellingShingle pyrimidines
anticancer activity
single-crystal X-ray diffraction
Technology
T
Electrical engineering. Electronics. Nuclear engineering
TK1-9971
Engineering (General). Civil engineering (General)
TA1-2040
Microscopy
QH201-278.5
Descriptive and experimental mechanics
QC120-168.85
Marcin Stolarczyk
Agnieszka Matera-Witkiewicz
Aleksandra Wolska
Magdalena Krupińska
Aleksandra Mikołajczyk
Anna Pyra
Iwona Bryndal
Synthesis, Crystal Structure, and Biological Evaluation of Novel 5-Hydroxymethylpyrimidines
description Pyrimidine displays a wide array of bioactivities, and thence, it is still considered a potent unit of new drug research. Its derivative, 5-hydroxymethylpyrimidine, can be found as a scaffold of nontypical nitrogen bases in DNA and as a core of some natural bioactive compounds. In this study, we obtained a series of 5-hydroxymethylpyrimidines that vary in the 4-position by the reduction of proper esters. All compounds were characterized by spectroscopic analysis, and single-crystal X-ray diffraction was performed for some of them. Biological investigations estimated cytotoxic properties against normal (RPTEC) and cancer (HeLa, HepaRG, Caco-2, AGS, A172) cell lines. It was found that the derivatives with an aliphatic amino group at the 4-position are generally less toxic to normal cells than those with a benzylsulfanyl group. Moreover, compounds with bulky constituents exhibit better anticancer properties, though at a moderate level. The specific compounds were chosen due to their most promising IC50 concentration for in silico study. Furthermore, antimicrobial activity tests were performed against six strains of bacteria and one fungus. They demonstrated that only derivatives with at least three carbon chain amino groups at the 4-position have weak antibacterial properties, and only the derivative with 4-benzylsulfanyl constituent exhibits any antifungal action.
format article
author Marcin Stolarczyk
Agnieszka Matera-Witkiewicz
Aleksandra Wolska
Magdalena Krupińska
Aleksandra Mikołajczyk
Anna Pyra
Iwona Bryndal
author_facet Marcin Stolarczyk
Agnieszka Matera-Witkiewicz
Aleksandra Wolska
Magdalena Krupińska
Aleksandra Mikołajczyk
Anna Pyra
Iwona Bryndal
author_sort Marcin Stolarczyk
title Synthesis, Crystal Structure, and Biological Evaluation of Novel 5-Hydroxymethylpyrimidines
title_short Synthesis, Crystal Structure, and Biological Evaluation of Novel 5-Hydroxymethylpyrimidines
title_full Synthesis, Crystal Structure, and Biological Evaluation of Novel 5-Hydroxymethylpyrimidines
title_fullStr Synthesis, Crystal Structure, and Biological Evaluation of Novel 5-Hydroxymethylpyrimidines
title_full_unstemmed Synthesis, Crystal Structure, and Biological Evaluation of Novel 5-Hydroxymethylpyrimidines
title_sort synthesis, crystal structure, and biological evaluation of novel 5-hydroxymethylpyrimidines
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/68f751a1eae340b89839a40e4edb3d00
work_keys_str_mv AT marcinstolarczyk synthesiscrystalstructureandbiologicalevaluationofnovel5hydroxymethylpyrimidines
AT agnieszkamaterawitkiewicz synthesiscrystalstructureandbiologicalevaluationofnovel5hydroxymethylpyrimidines
AT aleksandrawolska synthesiscrystalstructureandbiologicalevaluationofnovel5hydroxymethylpyrimidines
AT magdalenakrupinska synthesiscrystalstructureandbiologicalevaluationofnovel5hydroxymethylpyrimidines
AT aleksandramikołajczyk synthesiscrystalstructureandbiologicalevaluationofnovel5hydroxymethylpyrimidines
AT annapyra synthesiscrystalstructureandbiologicalevaluationofnovel5hydroxymethylpyrimidines
AT iwonabryndal synthesiscrystalstructureandbiologicalevaluationofnovel5hydroxymethylpyrimidines
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