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Open AccessArticle

Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH2 Core and Evaluation of Their Anticancer Activity

1
Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany
2
Department of Engineering and Natural Sciences, University of Applied Sciences Merseburg, Eberhard-Leibnitz-Strasse 2, 06217 Merseburg, Germany
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(2), 59; https://doi.org/10.3390/pharmaceutics11020059
Received: 10 October 2018 / Revised: 15 January 2019 / Accepted: 23 January 2019 / Published: 1 February 2019
(This article belongs to the Special Issue Dendrimers in Nanomedical Applications: Update and Future Directions)
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-NH2) dendrimers with the simultaneous introduction of lipidic (i-Pr) and cationic (–NH2) 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 –NH2 (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. View Full-Text
Keywords: cell type selective uptake; anticancer drugs; PAMAM-NH2 dendrimer; chlorambucil; Ugi reaction; non-cancerous mouse NIH3T3 fibroblasts; PC-3 prostate cancer cell; HT-29 colon cancer cell; multicomponent reaction cell type selective uptake; anticancer drugs; PAMAM-NH2 dendrimer; chlorambucil; Ugi reaction; non-cancerous mouse NIH3T3 fibroblasts; PC-3 prostate cancer cell; HT-29 colon cancer cell; multicomponent reaction
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MDPI and ACS Style

Seixas, N.; Ravanello, B.B.; Morgan, I.; Kaluđerović, G.N.; Wessjohann, L.A. Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH2 Core and Evaluation of Their Anticancer Activity. Pharmaceutics 2019, 11, 59. https://doi.org/10.3390/pharmaceutics11020059

AMA Style

Seixas N, Ravanello BB, Morgan I, Kaluđerović GN, Wessjohann LA. Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH2 Core and Evaluation of Their Anticancer Activity. Pharmaceutics. 2019; 11(2):59. https://doi.org/10.3390/pharmaceutics11020059

Chicago/Turabian Style

Seixas, Nalin; Ravanello, Bruno B.; Morgan, Ibrahim; Kaluđerović, Goran N.; Wessjohann, Ludger A. 2019. "Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH2 Core and Evaluation of Their Anticancer Activity" Pharmaceutics 11, no. 2: 59. https://doi.org/10.3390/pharmaceutics11020059

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