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Three-Component Reaction of Diamines with Triethyl Orthoformate and Diethyl Phosphite and Anti-Proliferative and Antiosteoporotic Activities of the Products

A three-component reaction between diamines (diaminobenzenes, diaminocyclohexanes, and piperazines), triethyl orthoformate, and diethyl phosphite was studied in some detail. In the case of 1,3- and 1,4-diamines and piperazines, products of the substitution of two amino moieties—the corresponding tet...

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Autores principales: Petruczynik, Patrycja, Kafarski, Paweł, Psurski, Mateusz, Wietrzyk, Joanna, Kiełbowicz, Zdzisław, Kuryszko, Jan, Chmielewska, Ewa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144383/
https://www.ncbi.nlm.nih.gov/pubmed/32245019
http://dx.doi.org/10.3390/molecules25061424
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author Petruczynik, Patrycja
Kafarski, Paweł
Psurski, Mateusz
Wietrzyk, Joanna
Kiełbowicz, Zdzisław
Kuryszko, Jan
Chmielewska, Ewa
author_facet Petruczynik, Patrycja
Kafarski, Paweł
Psurski, Mateusz
Wietrzyk, Joanna
Kiełbowicz, Zdzisław
Kuryszko, Jan
Chmielewska, Ewa
author_sort Petruczynik, Patrycja
collection PubMed
description A three-component reaction between diamines (diaminobenzenes, diaminocyclohexanes, and piperazines), triethyl orthoformate, and diethyl phosphite was studied in some detail. In the case of 1,3- and 1,4-diamines and piperazines, products of the substitution of two amino moieties—the corresponding tetraphosphonic acids—were obtained. In the cases of 1,2-diaminobenzene, 1,2-diaminocyclohexanes and 1,2-diaminocyclohexenes, only one amino group reacted. This is most likely the result of the formation of hydrogen bonding between the phosphonate oxygen and a hydrogen of the adjacent amino group, which caused a decrease in the reactivity of the amino group. Most of the obtained compounds inhibited the proliferation of RAW 264.7 macrophages, PC-3 human prostate cancer cells, and MCF-7 human breast cancer cells, with 1, trans-7, and 16 showing broad nonspecific activity, which makes these compounds especially interesting in the context of anti-osteolytic treatment and the blocking of interactions and mutual activation of osteoclasts and tumor metastatic cells. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid, which were used as controls. However, studies of sheep with induced osteoporosis carried out with compound trans-7 did not support this assumption.
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spelling pubmed-71443832020-04-13 Three-Component Reaction of Diamines with Triethyl Orthoformate and Diethyl Phosphite and Anti-Proliferative and Antiosteoporotic Activities of the Products Petruczynik, Patrycja Kafarski, Paweł Psurski, Mateusz Wietrzyk, Joanna Kiełbowicz, Zdzisław Kuryszko, Jan Chmielewska, Ewa Molecules Article A three-component reaction between diamines (diaminobenzenes, diaminocyclohexanes, and piperazines), triethyl orthoformate, and diethyl phosphite was studied in some detail. In the case of 1,3- and 1,4-diamines and piperazines, products of the substitution of two amino moieties—the corresponding tetraphosphonic acids—were obtained. In the cases of 1,2-diaminobenzene, 1,2-diaminocyclohexanes and 1,2-diaminocyclohexenes, only one amino group reacted. This is most likely the result of the formation of hydrogen bonding between the phosphonate oxygen and a hydrogen of the adjacent amino group, which caused a decrease in the reactivity of the amino group. Most of the obtained compounds inhibited the proliferation of RAW 264.7 macrophages, PC-3 human prostate cancer cells, and MCF-7 human breast cancer cells, with 1, trans-7, and 16 showing broad nonspecific activity, which makes these compounds especially interesting in the context of anti-osteolytic treatment and the blocking of interactions and mutual activation of osteoclasts and tumor metastatic cells. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid, which were used as controls. However, studies of sheep with induced osteoporosis carried out with compound trans-7 did not support this assumption. MDPI 2020-03-20 /pmc/articles/PMC7144383/ /pubmed/32245019 http://dx.doi.org/10.3390/molecules25061424 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Petruczynik, Patrycja
Kafarski, Paweł
Psurski, Mateusz
Wietrzyk, Joanna
Kiełbowicz, Zdzisław
Kuryszko, Jan
Chmielewska, Ewa
Three-Component Reaction of Diamines with Triethyl Orthoformate and Diethyl Phosphite and Anti-Proliferative and Antiosteoporotic Activities of the Products
title Three-Component Reaction of Diamines with Triethyl Orthoformate and Diethyl Phosphite and Anti-Proliferative and Antiosteoporotic Activities of the Products
title_full Three-Component Reaction of Diamines with Triethyl Orthoformate and Diethyl Phosphite and Anti-Proliferative and Antiosteoporotic Activities of the Products
title_fullStr Three-Component Reaction of Diamines with Triethyl Orthoformate and Diethyl Phosphite and Anti-Proliferative and Antiosteoporotic Activities of the Products
title_full_unstemmed Three-Component Reaction of Diamines with Triethyl Orthoformate and Diethyl Phosphite and Anti-Proliferative and Antiosteoporotic Activities of the Products
title_short Three-Component Reaction of Diamines with Triethyl Orthoformate and Diethyl Phosphite and Anti-Proliferative and Antiosteoporotic Activities of the Products
title_sort three-component reaction of diamines with triethyl orthoformate and diethyl phosphite and anti-proliferative and antiosteoporotic activities of the products
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144383/
https://www.ncbi.nlm.nih.gov/pubmed/32245019
http://dx.doi.org/10.3390/molecules25061424
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