Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Seixas, Nalin, Ravanello, Bruno B., Morgan, Ibrahim, Kaluđerović, Goran N., Wessjohann, Ludger A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783402065836376064
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
work_keys_str_mv AT seixasnalin chlorambucilconjugatedugidendrimerswithpamamnh2coreandevaluationoftheiranticanceractivity
AT ravanellobrunob chlorambucilconjugatedugidendrimerswithpamamnh2coreandevaluationoftheiranticanceractivity
AT morganibrahim chlorambucilconjugatedugidendrimerswithpamamnh2coreandevaluationoftheiranticanceractivity
AT kaluđerovicgorann chlorambucilconjugatedugidendrimerswithpamamnh2coreandevaluationoftheiranticanceractivity
AT wessjohannludgera chlorambucilconjugatedugidendrimerswithpamamnh2coreandevaluationoftheiranticanceractivity