An impact of 1H-indol-4-, -5-, -6-, -7-ylamines-substituted compounds on the microbial cell genetic apparatus

The study of new antimicrobial compounds includes determining the mechanism of their effect on the microbial cell. As a rule, an effect for the majority of current synthetic antimicrobials is associated either with suppressed DNA synthesis, or with inhibiting bacterial protein production at translat...

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Autores principales:	A. A. Maseykina, I. S. Stepanenko, S. A. Yamashkin, E. D. Slastnikov
Formato:	article
Lenguaje:	RU
Publicado:	Sankt-Peterburg : NIIÈM imeni Pastera 2021
Materias:	sos chromotest alkaline phosphatase β-galactosidase activity induction factor of the sos response of a cell genotoxicity antibacterial activity Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/78433b5ab71f45bb97f9d6476d412f23
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spelling	oai:doaj.org-article:78433b5ab71f45bb97f9d6476d412f232021-11-22T07:09:55ZAn impact of 1H-indol-4-, -5-, -6-, -7-ylamines-substituted compounds on the microbial cell genetic apparatus2220-76192313-739810.15789/2220-7619-TEO-1451https://doaj.org/article/78433b5ab71f45bb97f9d6476d412f232021-09-01T00:00:00Zhttps://www.iimmun.ru/iimm/article/view/1451https://doaj.org/toc/2220-7619https://doaj.org/toc/2313-7398The study of new antimicrobial compounds includes determining the mechanism of their effect on the microbial cell. As a rule, an effect for the majority of current synthetic antimicrobials is associated either with suppressed DNA synthesis, or with inhibiting bacterial protein production at translational or transcriptional level. A number of sensitive and easy-todo methods are available for screening and monitoring potential genotoxic activity of a wide range of natural and synthetic compounds. To date, the Ames test has been widely used, which is based on the sensitivity of Salmonella strains to carcinogenic chemicals, although some compounds resulting in Ames negative reactions could actually be carcinogenic to animals. Likewise, the SOS chromotest represents a SOS transcriptional analysis able to assess DNA damage caused by chemical and physical mutagens by measuring the expression of a reporter gene (β-galactosidase) encoding the β-galactosidase enzyme that metabolizes ortho-nitrophenyl galactopyranoside resulting in emerging a yellow-colored compound detected at wavelength 420 nm. Next, the induction of β-galactosidase is normalized by the activity of alkaline phosphatase, an enzyme expressed constitutively by Escherichia coli. SOS chromotest is also widely used for genotoxicological studies providing a quick answer (several hours) and requiring no survival of the test strain. Dose-response curves for various chemicals consist of a linear region, which slope corresponds to the SOS induction. Therefore, the SOS chromotest was selected for the study allowing to identify DNA-mediated effects of the analyzed compounds. The aim of the study was to evaluate the SOSinducing activity for 1H-indol-4-, -5-, -6-, -7-ylamines-substituted antimicrobial compounds. The Escherichia coli PQ 37 with the genotype F-thr leu his-4 pyrD thi galE lacΔU169 srl300::Th10 rpoB rpsL uvrA rfa trp::Mis+ sfiA:: Mud (Ar, lac) cts was used as a test strain. Due to the link of the sfi A::lac Z genes, lacZ β-galactosidase gene expression in the strain PQ 37 is controlled by the sfiA gene promoter, one of the components in the E. coli SOS regulon. Activity of β-galactosidase assessed relative to constitutive microbial alkaline phosphatase reflects SOS-inducing activity triggered by examined compounds in the SOS chromotest that also allows to control their toxic effects on bacterial cells. The data showed that 4,4,4-trifluoroN-(6-methoxy-1,2,3-trimethyl-1H-indol-5-yl)-3-oxobutanamide (1), 4,4,4-trifluoro-N-(6-methyl-2-phenyl-1H-indol-5-yl)- 3-oxobutanamide (2) and N-(1,5-dimethyl-2-phenyl-1H-indol-6-yl)-4,4,4-trifluoro-3-oxobutanamide (3) exerted no SOSinducing activity at the examined concentrations. In contrast, 4-Hydroxy-8-phenyl-4-(trifluoromethyl)-1,3,4,7-tetrahydro- 2H-pyrrolo [2,3-h]-quinoliN-2-one (4), 9-hydroxy-5-methyl-2-phenyl-9-(trifluoromethyl)-1,6,8,9-tetrahydro-7Н-pyrrolo- [2,3-f]-quinoliN-7-one (5), 6-hydroxy-2,3-dimethyl-6-(trifluoromethyl)-1,6,7,9-tetrahydro-8H-pyrrolo[3,2-h]quinoliN-8- one (6) and 1,2,3,9-tetramethyl-6-(trifluoromethyl)-1,9-dihydro-8H-pyrrolo [3,2-h]-quinoliN-8-one (7) displayed a dosedependent SOS-inducing activity at bactericidal concentrations. The data obtained allowed us to identify compounds 4, 5, 6, 7, which mechanism of action relies on affecting microbial cell DNA.A. A. MaseykinaI. S. StepanenkoS. A. YamashkinE. D. SlastnikovSankt-Peterburg : NIIÈM imeni Pasteraarticlesos chromotestalkaline phosphataseβ-galactosidase activityinduction factor of the sos response of a cellgenotoxicityantibacterial activityInfectious and parasitic diseasesRC109-216RUInfekciâ i Immunitet, Vol 11, Iss 4, Pp 663-670 (2021)
institution	DOAJ
collection	DOAJ
language	RU
topic	sos chromotest alkaline phosphatase β-galactosidase activity induction factor of the sos response of a cell genotoxicity antibacterial activity Infectious and parasitic diseases RC109-216
spellingShingle	sos chromotest alkaline phosphatase β-galactosidase activity induction factor of the sos response of a cell genotoxicity antibacterial activity Infectious and parasitic diseases RC109-216 A. A. Maseykina I. S. Stepanenko S. A. Yamashkin E. D. Slastnikov An impact of 1H-indol-4-, -5-, -6-, -7-ylamines-substituted compounds on the microbial cell genetic apparatus
description	The study of new antimicrobial compounds includes determining the mechanism of their effect on the microbial cell. As a rule, an effect for the majority of current synthetic antimicrobials is associated either with suppressed DNA synthesis, or with inhibiting bacterial protein production at translational or transcriptional level. A number of sensitive and easy-todo methods are available for screening and monitoring potential genotoxic activity of a wide range of natural and synthetic compounds. To date, the Ames test has been widely used, which is based on the sensitivity of Salmonella strains to carcinogenic chemicals, although some compounds resulting in Ames negative reactions could actually be carcinogenic to animals. Likewise, the SOS chromotest represents a SOS transcriptional analysis able to assess DNA damage caused by chemical and physical mutagens by measuring the expression of a reporter gene (β-galactosidase) encoding the β-galactosidase enzyme that metabolizes ortho-nitrophenyl galactopyranoside resulting in emerging a yellow-colored compound detected at wavelength 420 nm. Next, the induction of β-galactosidase is normalized by the activity of alkaline phosphatase, an enzyme expressed constitutively by Escherichia coli. SOS chromotest is also widely used for genotoxicological studies providing a quick answer (several hours) and requiring no survival of the test strain. Dose-response curves for various chemicals consist of a linear region, which slope corresponds to the SOS induction. Therefore, the SOS chromotest was selected for the study allowing to identify DNA-mediated effects of the analyzed compounds. The aim of the study was to evaluate the SOSinducing activity for 1H-indol-4-, -5-, -6-, -7-ylamines-substituted antimicrobial compounds. The Escherichia coli PQ 37 with the genotype F-thr leu his-4 pyrD thi galE lacΔU169 srl300::Th10 rpoB rpsL uvrA rfa trp::Mis+ sfiA:: Mud (Ar, lac) cts was used as a test strain. Due to the link of the sfi A::lac Z genes, lacZ β-galactosidase gene expression in the strain PQ 37 is controlled by the sfiA gene promoter, one of the components in the E. coli SOS regulon. Activity of β-galactosidase assessed relative to constitutive microbial alkaline phosphatase reflects SOS-inducing activity triggered by examined compounds in the SOS chromotest that also allows to control their toxic effects on bacterial cells. The data showed that 4,4,4-trifluoroN-(6-methoxy-1,2,3-trimethyl-1H-indol-5-yl)-3-oxobutanamide (1), 4,4,4-trifluoro-N-(6-methyl-2-phenyl-1H-indol-5-yl)- 3-oxobutanamide (2) and N-(1,5-dimethyl-2-phenyl-1H-indol-6-yl)-4,4,4-trifluoro-3-oxobutanamide (3) exerted no SOSinducing activity at the examined concentrations. In contrast, 4-Hydroxy-8-phenyl-4-(trifluoromethyl)-1,3,4,7-tetrahydro- 2H-pyrrolo [2,3-h]-quinoliN-2-one (4), 9-hydroxy-5-methyl-2-phenyl-9-(trifluoromethyl)-1,6,8,9-tetrahydro-7Н-pyrrolo- [2,3-f]-quinoliN-7-one (5), 6-hydroxy-2,3-dimethyl-6-(trifluoromethyl)-1,6,7,9-tetrahydro-8H-pyrrolo[3,2-h]quinoliN-8- one (6) and 1,2,3,9-tetramethyl-6-(trifluoromethyl)-1,9-dihydro-8H-pyrrolo [3,2-h]-quinoliN-8-one (7) displayed a dosedependent SOS-inducing activity at bactericidal concentrations. The data obtained allowed us to identify compounds 4, 5, 6, 7, which mechanism of action relies on affecting microbial cell DNA.
format	article
author	A. A. Maseykina I. S. Stepanenko S. A. Yamashkin E. D. Slastnikov
author_facet	A. A. Maseykina I. S. Stepanenko S. A. Yamashkin E. D. Slastnikov
author_sort	A. A. Maseykina
title	An impact of 1H-indol-4-, -5-, -6-, -7-ylamines-substituted compounds on the microbial cell genetic apparatus
title_short	An impact of 1H-indol-4-, -5-, -6-, -7-ylamines-substituted compounds on the microbial cell genetic apparatus
title_full	An impact of 1H-indol-4-, -5-, -6-, -7-ylamines-substituted compounds on the microbial cell genetic apparatus
title_fullStr	An impact of 1H-indol-4-, -5-, -6-, -7-ylamines-substituted compounds on the microbial cell genetic apparatus
title_full_unstemmed	An impact of 1H-indol-4-, -5-, -6-, -7-ylamines-substituted compounds on the microbial cell genetic apparatus
title_sort	impact of 1h-indol-4-, -5-, -6-, -7-ylamines-substituted compounds on the microbial cell genetic apparatus
publisher	Sankt-Peterburg : NIIÈM imeni Pastera
publishDate	2021
url	https://doaj.org/article/78433b5ab71f45bb97f9d6476d412f23
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An impact of 1H-indol-4-, -5-, -6-, -7-ylamines-substituted compounds on the microbial cell genetic apparatus

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