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Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH(2) Core and Evaluation of Their Anticancer Activity
Herein, a new Ugi multicomponent reaction strategy is described to enhance activity and solubility of the chemotherapeutic drug chlorambucil through its conjugation to poly(amidoamine) (PAMAM-NH(2)) dendrimers with the simultaneous introduction of lipidic (i-Pr) and cationic (–NH(2)) or anionic (–CO...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409784/ https://www.ncbi.nlm.nih.gov/pubmed/30717083 http://dx.doi.org/10.3390/pharmaceutics11020059 |
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author | Seixas, Nalin Ravanello, Bruno B. Morgan, Ibrahim Kaluđerović, Goran N. Wessjohann, Ludger A. |
author_facet | Seixas, Nalin Ravanello, Bruno B. Morgan, Ibrahim Kaluđerović, Goran N. Wessjohann, Ludger A. |
author_sort | Seixas, Nalin |
collection | PubMed |
description | Herein, a new Ugi multicomponent reaction strategy is described to enhance activity and solubility of the chemotherapeutic drug chlorambucil through its conjugation to poly(amidoamine) (PAMAM-NH(2)) dendrimers with the simultaneous introduction of lipidic (i-Pr) and cationic (–NH(2)) or anionic (–COOH) groups. Standard viability assays were used to evaluate the anticancer potential of the water-soluble dendrimers against PC-3 prostate and HT-29 colon cancer cell lines, as well as non-cancerous mouse NIH3T3 fibroblasts. It could be demonstrated that the anticancer activity against PC-3 cells was considerably improved when both chlorambucil and –NH(2) (cationic) groups were present on the dendrimer surface (1b). Additionally, this dendrimer showed activity only against the prostate cancer cells (PC-3), while it did not affect colon cancer cells and fibroblasts significantly. The cationic chlorambucil-dendrimer 1b blocks PC-3 cells in the G2/M phase and induces caspase independent apoptosis. |
format | Online Article Text |
id | pubmed-6409784 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64097842019-03-29 Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH(2) Core and Evaluation of Their Anticancer Activity Seixas, Nalin Ravanello, Bruno B. Morgan, Ibrahim Kaluđerović, Goran N. Wessjohann, Ludger A. Pharmaceutics Article Herein, a new Ugi multicomponent reaction strategy is described to enhance activity and solubility of the chemotherapeutic drug chlorambucil through its conjugation to poly(amidoamine) (PAMAM-NH(2)) dendrimers with the simultaneous introduction of lipidic (i-Pr) and cationic (–NH(2)) or anionic (–COOH) groups. Standard viability assays were used to evaluate the anticancer potential of the water-soluble dendrimers against PC-3 prostate and HT-29 colon cancer cell lines, as well as non-cancerous mouse NIH3T3 fibroblasts. It could be demonstrated that the anticancer activity against PC-3 cells was considerably improved when both chlorambucil and –NH(2) (cationic) groups were present on the dendrimer surface (1b). Additionally, this dendrimer showed activity only against the prostate cancer cells (PC-3), while it did not affect colon cancer cells and fibroblasts significantly. The cationic chlorambucil-dendrimer 1b blocks PC-3 cells in the G2/M phase and induces caspase independent apoptosis. MDPI 2019-02-01 /pmc/articles/PMC6409784/ /pubmed/30717083 http://dx.doi.org/10.3390/pharmaceutics11020059 Text en © 2019 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 Seixas, Nalin Ravanello, Bruno B. Morgan, Ibrahim Kaluđerović, Goran N. Wessjohann, Ludger A. Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH(2) Core and Evaluation of Their Anticancer Activity |
title | Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH(2) Core and Evaluation of Their Anticancer Activity |
title_full | Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH(2) Core and Evaluation of Their Anticancer Activity |
title_fullStr | Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH(2) Core and Evaluation of Their Anticancer Activity |
title_full_unstemmed | Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH(2) Core and Evaluation of Their Anticancer Activity |
title_short | Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH(2) Core and Evaluation of Their Anticancer Activity |
title_sort | chlorambucil conjugated ugi dendrimers with pamam-nh(2) core and evaluation of their anticancer activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409784/ https://www.ncbi.nlm.nih.gov/pubmed/30717083 http://dx.doi.org/10.3390/pharmaceutics11020059 |
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