Identification of Spiro-Fused Pyrrolo[3,4-<i>a</i>]pyrrolizines and Tryptanthrines as Potential Antitumor Agents: Synthesis and In Vitro Evaluation

A series of heterocyclic compounds containing a spiro-fused pyrrolo[3,4-<i>a</i>]pyrrolizine and tryptanthrin framework have been synthesized and studied as potential antitumor agents. Cytotoxicity of products was screened against human erythroleukemia (K562) and human cervical carcinoma...

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Autores principales:	Diana K. Latypova, Stanislav V. Shmakov, Sofya A. Pechkovskaya, Alexander S. Filatov, Alexander V. Stepakov, Nickolay A. Knyazev, Vitali M. Boitsov
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	one-pot synthesis 1,3-dipolar cycloaddition tryptanthrin-derived azomethine ylide pyrrolo[3,4-<i>a</i>]pyrrolizine tumor cells antiproliferative activity Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/93d8c4d3ad054ca4a3382215286f5fee
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spelling	oai:doaj.org-article:93d8c4d3ad054ca4a3382215286f5fee2021-11-11T17:24:46ZIdentification of Spiro-Fused Pyrrolo[3,4-<i>a</i>]pyrrolizines and Tryptanthrines as Potential Antitumor Agents: Synthesis and In Vitro Evaluation10.3390/ijms2221119971422-00671661-6596https://doaj.org/article/93d8c4d3ad054ca4a3382215286f5fee2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11997https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067A series of heterocyclic compounds containing a spiro-fused pyrrolo[3,4-<i>a</i>]pyrrolizine and tryptanthrin framework have been synthesized and studied as potential antitumor agents. Cytotoxicity of products was screened against human erythroleukemia (K562) and human cervical carcinoma (HeLa) cell lines. Among the screened compounds. <b>4a</b>, <b>4b</b> and <b>5a</b> were active against human erythroleukemia (K562) cell line, while <b>4a</b> and <b>5a</b> were active against cervical carcinoma (HeLa) cell line. In agreement with the DNA cytometry studies, the tested compounds have achieved significant cell-cycle perturbation with higher accumulation of cells in G2/M phase and induced apoptosis. Using confocal microscopy, we found that with <b>4a</b> and <b>5a</b> treatment of HeLa cells, actin filaments disappeared, and granular actin was distributed diffusely in the cytoplasm in 76–91% of cells. We discovered that HeLa cells after treatment with compounds <b>4a</b> and <b>5a</b> significantly reduced the number of cells with filopodium-like membrane protrusions (from 63 % in control cells to 29% after treatment) and a decrease in cell motility.Diana K. LatypovaStanislav V. ShmakovSofya A. PechkovskayaAlexander S. FilatovAlexander V. StepakovNickolay A. KnyazevVitali M. BoitsovMDPI AGarticleone-pot synthesis1,3-dipolar cycloadditiontryptanthrin-derived azomethine ylidepyrrolo[3,4-<i>a</i>]pyrrolizinetumor cellsantiproliferative activityBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11997, p 11997 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	one-pot synthesis 1,3-dipolar cycloaddition tryptanthrin-derived azomethine ylide pyrrolo[3,4-<i>a</i>]pyrrolizine tumor cells antiproliferative activity Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	one-pot synthesis 1,3-dipolar cycloaddition tryptanthrin-derived azomethine ylide pyrrolo[3,4-<i>a</i>]pyrrolizine tumor cells antiproliferative activity Biology (General) QH301-705.5 Chemistry QD1-999 Diana K. Latypova Stanislav V. Shmakov Sofya A. Pechkovskaya Alexander S. Filatov Alexander V. Stepakov Nickolay A. Knyazev Vitali M. Boitsov Identification of Spiro-Fused Pyrrolo[3,4-<i>a</i>]pyrrolizines and Tryptanthrines as Potential Antitumor Agents: Synthesis and In Vitro Evaluation
description	A series of heterocyclic compounds containing a spiro-fused pyrrolo[3,4-<i>a</i>]pyrrolizine and tryptanthrin framework have been synthesized and studied as potential antitumor agents. Cytotoxicity of products was screened against human erythroleukemia (K562) and human cervical carcinoma (HeLa) cell lines. Among the screened compounds. <b>4a</b>, <b>4b</b> and <b>5a</b> were active against human erythroleukemia (K562) cell line, while <b>4a</b> and <b>5a</b> were active against cervical carcinoma (HeLa) cell line. In agreement with the DNA cytometry studies, the tested compounds have achieved significant cell-cycle perturbation with higher accumulation of cells in G2/M phase and induced apoptosis. Using confocal microscopy, we found that with <b>4a</b> and <b>5a</b> treatment of HeLa cells, actin filaments disappeared, and granular actin was distributed diffusely in the cytoplasm in 76–91% of cells. We discovered that HeLa cells after treatment with compounds <b>4a</b> and <b>5a</b> significantly reduced the number of cells with filopodium-like membrane protrusions (from 63 % in control cells to 29% after treatment) and a decrease in cell motility.
format	article
author	Diana K. Latypova Stanislav V. Shmakov Sofya A. Pechkovskaya Alexander S. Filatov Alexander V. Stepakov Nickolay A. Knyazev Vitali M. Boitsov
author_facet	Diana K. Latypova Stanislav V. Shmakov Sofya A. Pechkovskaya Alexander S. Filatov Alexander V. Stepakov Nickolay A. Knyazev Vitali M. Boitsov
author_sort	Diana K. Latypova
title	Identification of Spiro-Fused Pyrrolo[3,4-<i>a</i>]pyrrolizines and Tryptanthrines as Potential Antitumor Agents: Synthesis and In Vitro Evaluation
title_short	Identification of Spiro-Fused Pyrrolo[3,4-<i>a</i>]pyrrolizines and Tryptanthrines as Potential Antitumor Agents: Synthesis and In Vitro Evaluation
title_full	Identification of Spiro-Fused Pyrrolo[3,4-<i>a</i>]pyrrolizines and Tryptanthrines as Potential Antitumor Agents: Synthesis and In Vitro Evaluation
title_fullStr	Identification of Spiro-Fused Pyrrolo[3,4-<i>a</i>]pyrrolizines and Tryptanthrines as Potential Antitumor Agents: Synthesis and In Vitro Evaluation
title_full_unstemmed	Identification of Spiro-Fused Pyrrolo[3,4-<i>a</i>]pyrrolizines and Tryptanthrines as Potential Antitumor Agents: Synthesis and In Vitro Evaluation
title_sort	identification of spiro-fused pyrrolo[3,4-<i>a</i>]pyrrolizines and tryptanthrines as potential antitumor agents: synthesis and in vitro evaluation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/93d8c4d3ad054ca4a3382215286f5fee
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Identification of Spiro-Fused Pyrrolo[3,4-<i>a</i>]pyrrolizines and Tryptanthrines as Potential Antitumor Agents: Synthesis and In Vitro Evaluation

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