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An efficient synthesis of indolo[2,3-b]quinoline guanidine derivatives with their in vitro and in vivo study
An optimization of the guanidylation process by verifying the efficacy of common guanylation reagents in order to obtain the guanidine derivatives of indolo[2,3-b]quinoline has been performed. As a result, a high-yield procedure using N,N′-di-Boc-N′′-triflylguanidine was applied to synthesize the gu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676820/ https://www.ncbi.nlm.nih.gov/pubmed/29170613 http://dx.doi.org/10.1007/s00044-017-2028-1 |
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author | Sidoryk, Katarzyna Świtalska, Marta Rózga, Piotr Wietrzyk, Joanna Bujak, Iwona Żerek, Bartłomiej Kaczmarek, Łukasz Cybulski, Marcin |
author_facet | Sidoryk, Katarzyna Świtalska, Marta Rózga, Piotr Wietrzyk, Joanna Bujak, Iwona Żerek, Bartłomiej Kaczmarek, Łukasz Cybulski, Marcin |
author_sort | Sidoryk, Katarzyna |
collection | PubMed |
description | An optimization of the guanidylation process by verifying the efficacy of common guanylation reagents in order to obtain the guanidine derivatives of indolo[2,3-b]quinoline has been performed. As a result, a high-yield procedure using N,N′-di-Boc-N′′-triflylguanidine was applied to synthesize the guanidine derivative of indolo[2,3-b]quinoline 1 in a gram scale for specific in vitro and in vivo biological research. Extensive studies on the antiproliferative activity against eight human tumor cell lines were completed. Compound 1 revealed the highest activity against A549 lung adenocarcinoma and MCF7 breast cancer cell lines. Thus, 1 was evaluated for the in vivo anticancer activity against 4T1 mammary gland carcinoma and KLN205 murine lung carcinoma in mouse models. The anticancer effect was observed in the KLN205 model with a 37% tumor growth inhibition at the 20 mg/kg dose. This anticancer activity of 1 was comparable to that of cyclophosphamide which inhibited murine lung tumor growth in the range of 27–43% at the dose of 100 mg/kg. The biochemistry research after 1 admission, including measurements of blood parameters like alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and urea and creatinine, were also performed. |
format | Online Article Text |
id | pubmed-5676820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-56768202017-11-21 An efficient synthesis of indolo[2,3-b]quinoline guanidine derivatives with their in vitro and in vivo study Sidoryk, Katarzyna Świtalska, Marta Rózga, Piotr Wietrzyk, Joanna Bujak, Iwona Żerek, Bartłomiej Kaczmarek, Łukasz Cybulski, Marcin Med Chem Res Original Research An optimization of the guanidylation process by verifying the efficacy of common guanylation reagents in order to obtain the guanidine derivatives of indolo[2,3-b]quinoline has been performed. As a result, a high-yield procedure using N,N′-di-Boc-N′′-triflylguanidine was applied to synthesize the guanidine derivative of indolo[2,3-b]quinoline 1 in a gram scale for specific in vitro and in vivo biological research. Extensive studies on the antiproliferative activity against eight human tumor cell lines were completed. Compound 1 revealed the highest activity against A549 lung adenocarcinoma and MCF7 breast cancer cell lines. Thus, 1 was evaluated for the in vivo anticancer activity against 4T1 mammary gland carcinoma and KLN205 murine lung carcinoma in mouse models. The anticancer effect was observed in the KLN205 model with a 37% tumor growth inhibition at the 20 mg/kg dose. This anticancer activity of 1 was comparable to that of cyclophosphamide which inhibited murine lung tumor growth in the range of 27–43% at the dose of 100 mg/kg. The biochemistry research after 1 admission, including measurements of blood parameters like alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and urea and creatinine, were also performed. Springer US 2017-09-05 2017 /pmc/articles/PMC5676820/ /pubmed/29170613 http://dx.doi.org/10.1007/s00044-017-2028-1 Text en © The Author(s) 2017 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Research Sidoryk, Katarzyna Świtalska, Marta Rózga, Piotr Wietrzyk, Joanna Bujak, Iwona Żerek, Bartłomiej Kaczmarek, Łukasz Cybulski, Marcin An efficient synthesis of indolo[2,3-b]quinoline guanidine derivatives with their in vitro and in vivo study |
title | An efficient synthesis of indolo[2,3-b]quinoline guanidine derivatives with their in vitro and in vivo study |
title_full | An efficient synthesis of indolo[2,3-b]quinoline guanidine derivatives with their in vitro and in vivo study |
title_fullStr | An efficient synthesis of indolo[2,3-b]quinoline guanidine derivatives with their in vitro and in vivo study |
title_full_unstemmed | An efficient synthesis of indolo[2,3-b]quinoline guanidine derivatives with their in vitro and in vivo study |
title_short | An efficient synthesis of indolo[2,3-b]quinoline guanidine derivatives with their in vitro and in vivo study |
title_sort | efficient synthesis of indolo[2,3-b]quinoline guanidine derivatives with their in vitro and in vivo study |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676820/ https://www.ncbi.nlm.nih.gov/pubmed/29170613 http://dx.doi.org/10.1007/s00044-017-2028-1 |
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