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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Main Authors:	Marcin Stolarczyk, Agnieszka Matera-Witkiewicz, Aleksandra Wolska, Magdalena Krupińska, Aleksandra Mikołajczyk, Anna Pyra, Iwona Bryndal
Format:	article
Language:	EN
Published:	MDPI AG 2021
Subjects:	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
Online Access:	https://doaj.org/article/68f751a1eae340b89839a40e4edb3d00
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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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Synthesis, Crystal Structure, and Biological Evaluation of Novel 5-Hydroxymethylpyrimidines

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