Login Register Cart 0
Generic placeholder image

Current Organic Chemistry

Editor-in-Chief

ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis of Open-Resorcinarene Dendrimers with L-serine (Ibuprofen) Derivatives

Author(s): Luis Daniel Pedro-Hernández and Marcos Martínez-García*

Volume 26, Issue 1, 2022

Published on: 17 December, 2021

Page: [71 - 80] Pages: 10

DOI: 10.2174/1385272825666211130164548

Price: $65

conference banner
Abstract

A new class of dendrimers with open-resorcinarenes has been synthesized in good yields (77-85%). The open-resorcinarenes showed a high capacity for functionalization, having eight hydroxyl groups. The Williamson reaction with N,N-bis(2-azidoethyl)-2-bromo acetamide did not show any steric effect, obtaining sixteen azide terminal groups, which gave us the possibility to obtain a high molecular weight dendrimer via the azide-alkyne click reaction with prop-2-yn-1-yl-(ibuprofen)L-serinate derivatives to obtain the triazole ring spacers and the L-serinate(ibuprofen) derivatives as terminal groups. Also, we carried out the deprotection reaction of the L-serinate moiety terminal groups of the dendrimer 10 in good yields (95%). Three novel open-resorcinarene den-drimers with sixteen ibuprofen-L-serinate derivatives and hydroxyl, tert-butyl, and carboxylic acid; therefore, with three different terminal groups, with possible nanomedical activity are reported.

Keywords: Open-resorcinarenes, dendrimers, L-serine, ibuprofen, click reaction, triazole.

« Previous
Graphical Abstract

[1]
Tomalia, D.A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, P.A. A new class of polymers: Starburst-dendritic macromolecules. Polym. J., 1985, 17, 117-132.
[http://dx.doi.org/10.1295/polymj.17.117]
[2]
Tomalia, D.A. Birth of a new macromolecular architecture: Dendrimers as quantized building blocks for nanoscale synthetic organic chemistry. Aldrichim Acta, 2004, 37, 39-57.
[http://dx.doi.org/10.1016/j.progpolymsci.2005.01.007]
[3]
Ihre, H.; Padilla De Jesús, O.L.; Fréchet, J.M.J. Fast and convenient divergent synthesis of aliphatic ester dendrimers by anhydride coupling. J. Am. Chem. Soc., 2001, 123(25), 5908-5917.
[http://dx.doi.org/10.1021/ja010524e] [PMID: 11414823]
[4]
Menjoge, A.R.; Kannan, R.M.; Tomalia, D.A. Dendrimer-based drug and imaging conjugates: Design considerations for nanomedical applications. Drug Discov. Today, 2010, 15(5-6), 171-185.
[http://dx.doi.org/10.1016/j.drudis.2010.01.009] [PMID: 20116448]
[5]
Hardie, M.J. Recent advances in the chemistry of cyclotriveratrylene. Chem. Soc. Rev., 2010, 39(2), 516-527.
[http://dx.doi.org/10.1039/B821019P] [PMID: 20111776]
[6]
Marradi, M.; Cicchi, S.; Sansone, F.; Casnati, A.; Goti, A. Low-generation dendrimers with a calixarene core and based on a chiral C(2)-symmetric pyrrolidine as iminosugar mimics. Beilstein J. Org. Chem., 2012, 8, 951-957.
[http://dx.doi.org/10.3762/bjoc.8.107] [PMID: 23015845]
[7]
Pedro-Hernández, L.D.; Organista-Mateos, U.; Allende-Alarcón, L.I.; Martínez-Klimova, E.; Ramírez-Ápan, T.; Martínez-García, M. Improvement of the anticancer activity of chlorambucil and ibuprofen via conjugates Calix[4]arene. Med. Chem., 2020, 16, 984-990.
[http://dx.doi.org/10.2174/1573406415666190826162339] [PMID: 31448714]
[8]
Li, W.S.; Aida, T. Dendrimer porphyrins and phthalocyanines. Chem. Rev., 2009, 109(11), 6047-6076.
[http://dx.doi.org/10.1021/cr900186c] [PMID: 19769361]
[9]
Padilla-Monroy, S.; Martínez-Klimova, E.; Ramírez-Ápan, T.; Nieto-Camacho, A.; Calderón-Pardo, J.; Martínez-García, M. Porphyrin conjugates of ibuprofen and their antiproliferative activity against human prostate and breast cancer cells. Biointerface Res. Appl. Chem., 2018, 8, 3039-3048.
[10]
Pedro-Hernández, L.D.; Martínez-Klimova, E.; Cortez-Maya, S.; Mendoza-Cardozo, S.; Ramírez-Ápan, T.; Martínez-García, M. Synthesis, characterization and nanomedical applications of conjugates between resorcinarene-dendrimers and ibuprofen. Nanomaterials (Basel), 2017, 7(7), 163-173.
[http://dx.doi.org/10.3390/nano7070163] [PMID: 28665319]
[11]
Ge, Y.; Yan, C. Rapid synthesis of calix[4]resorcinarene-based dendrimers containing salicylideneimine terminal groups. J. Chem. Res., 2004, 4, 279-281.
[http://dx.doi.org/10.3184/0308234041209176]
[12]
Daniel Pedro-Hernández, L.; Hernández-Montalbán, C.; Martínez-Klimova, E.; Ramírez-Ápan, T.; Martínez-García, M. Synthesis and anticancer activity of open-resorcinarene conjugates. Bioorg. Med. Chem. Lett., 2020, 30(14)127275
[http://dx.doi.org/10.1016/j.bmcl.2020.127275] [PMID: 32527536]
[13]
Arseneault, M.; Wafer, C.; Morin, J.F. Recent advances in click chemistry applied to dendrimer synthesis. Molecules, 2015, 20(5), 9263-9294.
[http://dx.doi.org/10.3390/molecules20059263] [PMID: 26007183]
[14]
Hsu, H.J.; Bugno, J.; Lee, S.R.; Hong, S. Dendrimer-based nanocarriers: A versatile platform for drug delivery. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 2017, 9(1), 1.
[http://dx.doi.org/10.1002/wnan.1409] [PMID: 27126551]
[15]
Kuang, T.; Fu, D.; Chang, L.; Yang, Z.; Chen, Z.; Jin, L.; Chen, F.; Peng, X. Recent progress in dendrimer-based gene delivery systems. Curr. Org. Chem., 2016, 20, 1820-1826.
[http://dx.doi.org/10.2174/1385272820666151123235059]
[16]
Pérez, Y.A.; Urista, C.M.; Martínez, J.I.; Nava, M.D.C.D.; Rodríguez, F.A.R. Functionalized polymers for enhance oral bioavailability of sensitive molecules. Polymers (Basel), 2016, 8(6), 214.
[http://dx.doi.org/10.3390/polym8060214] [PMID: 30979310]
[17]
Esfand, R.; Tomalia, D.A. Poly(amidoamine) (PAMAM) dendrimers: From biomimicry to drug delivery and biomedical applications. Drug Discov. Today, 2001, 6(8), 427-436.
[http://dx.doi.org/10.1016/S1359-6446(01)01757-3] [PMID: 11301287]
[18]
Yao, M.; Zhou, W.; Sangha, S.; Albert, A.; Chang, A.J.; Liu, T.C.; Wolfe, M.M. Effects of nonselective cyclooxygenase inhibition with low-dose ibuprofen on tumor growth, angiogenesis, metastasis, and survival in a mouse model of colorectal cancer. Clin. Cancer Res., 2005, 11(4), 1618-1628.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-1696] [PMID: 15746067]
[19]
Yan, C.; Gu, J.; Hou, D.; Jing, H.; Wang, J.; Guo, Y.; Katsumi, H.; Sakane, T.; Yamamoto, A. Improved tumor targetability of Tat-conjugated PAMAM dendrimers as a novel nanosized anti-tumor drug carrier. Drug Dev. Ind. Pharm., 2015, 41(4), 617-622.
[http://dx.doi.org/10.3109/03639045.2014.891127] [PMID: 24564798]
[20]
Bhatt, H.; Ghosh, B.; Biswas, S. Cell-Penetrating peptide and α-Tocopherol-conjugated poly (amidoamine) dendrimers for improved delivery and anticancer activity of loaded paclitaxel. ACS Appl. Bio Mater., 2020, 3(5), 3157-3169.
[http://dx.doi.org/10.1021/acsabm.0c00179]
[21]
Somani, S.; Laskar, P.; Altwaijry, N.; Kewcharoenvong, P.; Irving, C.; Robb, G.; Pickard, B.S.; Dufès, C. PEGylation of polypropylenimine dendrimers: Effects on cytotoxicity, DNA condensation, gene delivery and expression in cancer cells. Sci. Rep., 2018, 8(1), 9410.
[http://dx.doi.org/10.1038/s41598-018-27400-6] [PMID: 29925967]
[22]
Zhang, M.; Zhu, J.; Zheng, Y.; Guo, R.; Wang, S.; Mignani, S.; Caminade, A.M.; Majoral, J.P.; Shi, X. Doxorubicin-conjugated PAMAM dendrimers for pH-responsive drug release and folic acid-targeted cancer therapy. Pharmaceutics, 2018, 10(3), 162.
[http://dx.doi.org/10.3390/pharmaceutics10030162] [PMID: 30235881]
[23]
Kurtoglu, Y.E.; Mishra, M.K.; Kannan, S.; Kannan, R.M. Drug release characteristics of PAMAM dendrimer-drug conjugates with different linkers. Int. J. Pharm., 2010, 384(1-2), 189-194.
[http://dx.doi.org/10.1016/j.ijpharm.2009.10.017] [PMID: 19825406]
[24]
Kudo, H.; Hayashi, R.; Mitani, K.; Yokozawa, T.; Kasuga, N.C.; Nishikubo, T. Molecular waterwheel (noria) from a simple condensation of resorcinol and an alkanedial. Angew. Chem. Int. Ed., 2006, 45(47), 7948-7952.
[http://dx.doi.org/10.1002/anie.200603013] [PMID: 17094148]
[25]
Cominetti, M.M.D.; Hughes, D.L.; Matthews, S.E. Open-resorcinarenes, a new family of multivalent scaffolds. Org. Biomol. Chem., 2016, 14(43), 10161-10164.
[http://dx.doi.org/10.1039/C6OB02164F] [PMID: 27735006]
[26]
Thakuria, R.; Sarma, B.; Nangia, A. Supramolecular networks of a H-shaped aromatic phenol host. New J. Chem., 2010, 34, 623-636.
[http://dx.doi.org/10.1039/B9NJ00234K]

Rights & Permissions Print Cite
Article Metrics
22
3
© 2024 Bentham Science Publishers | Privacy Policy