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 Dendrimer Conjugates with Naproxen and their Anticancer Activity

Author(s): Irving Osiel Castillo-Rodríguez, Teresa Ramírez-Ápan and Marcos Martínez-García*

Volume 27, Issue 6, 2023

Published on: 13 July, 2023

Page: [540 - 545] Pages: 6

DOI: 10.2174/1385272827666230605160243

Price: $65

Abstract

Here we report the easy synthesis of dendrimer conjugates with four and eight naproxen moieties at the periphery. The synthesis involved two steps protection-deprotection sequence joined with triethylene glycol. A comparison was made between the cytotoxicity of dendron-naproxen conjugates and that of G1.0 G2.0 dendrimer-naproxen conjugates. Cytotoxicity studies showed that dendron conjugates were toxic towards all cancer cell lines studied, and their toxicity was significantly lower than that of dendrimer conjugates. However, dendrimer conjugates showed higher cytotoxicity and selectivity against K-562 and SKLU- 1 than dendron conjugates.

Keywords: Dendrimers, anticancer activity, conjugates, naproxen, triethylene glycol, esterification reactions.

« Previous Next »
Graphical Abstract

[1]
Tomalia, D.A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, P. A new class of polymers: Starburst-dendritic macromolecules. Polym. J., 1985, 17(1), 117-132.
[http://dx.doi.org/10.1295/polymj.17.117]
[2]
D’Emanuele, A.; Attwood, D.; Abu-Rmaileh, R. Dendrimers.In: Encyclopedia of Pharmaceutical Technology; Swarbrick, J.B.J.C., Ed.; Marcel Dekker: New York, NY, USA, 2003, pp. 1-21.
[3]
Kesharwani, P.; Gothwal, A.; Iyer, A.K.; Jain, K.; Chourasia, M.K.; Gupta, U. Dendrimer nanohybrid carrier systems: An expanding horizon for targeted drug and gene delivery. Drug Discov. Today, 2018, 23(2), 300-314.
[http://dx.doi.org/10.1016/j.drudis.2017.06.009] [PMID: 28697371]
[4]
Natfji, A.A.; Osborn, H.M.I.; Greco, F. Feasibility of polymer-drug conjugates for non-cancer applications. Curr. Opin. Colloid Interface Sci., 2017, 31, 51-66.
[http://dx.doi.org/10.1016/j.cocis.2017.07.004]
[5]
Hsu, H.J.; Bugno, J.; Lee, S.; 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]
[6]
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(17), 1820-1826.
[http://dx.doi.org/10.2174/1385272820666151123235059]
[7]
Demanuele, A.; Attwood, D. Dendrimer–drug interactions. Adv. Drug Deliv. Rev., 2005, 57(15), 2147-2162.
[http://dx.doi.org/10.1016/j.addr.2005.09.012] [PMID: 16310283]
[8]
Milhem, O.M.; Myles, C.; McKeown, N.B.; Attwood, D.; D’Emanuele, A. Polyamidoamine Starburst® dendrimers as solubility enhancers. Int. J. Pharm., 2000, 197(1-2), 239-241.
[http://dx.doi.org/10.1016/S0378-5173(99)00463-9] [PMID: 10704811]
[9]
Yiyun, C.; Tongwen, X. Dendrimers as potential drug carriers. Part I. Solubilization of non-steroidal anti-inflammatory drugs in the presence of polyamidoamine den-drimers. Eur. J. Med. Chem., 2005, 40(11), 1188-1192.
[http://dx.doi.org/10.1016/j.ejmech.2005.06.010] [PMID: 16153746]
[10]
Nasr, M.; Najlah, M.; D’Emanuele, A.; Elhissi, A. PAMAM dendrimers as aerosol drug nanocarriers for pulmonary delivery via nebulization. Int. J. Pharm., 2014, 461(1-2), 242-250.
[http://dx.doi.org/10.1016/j.ijpharm.2013.11.023] [PMID: 24275446]
[11]
Venuganti, V.V.; Sahdev, P.; Hildreth, M.; Guan, X.; Perumal, O. Structure-skin permeability relationship of dendrimers. Pharm. Res., 2011, 28(9), 2246-2260.
[http://dx.doi.org/10.1007/s11095-011-0455-0] [PMID: 21633876]
[12]
Kolhatkar, R.B.; Kitchens, K.M.; Swaan, P.W.; Ghandehari, H. Surface acetylation of polyamidoamine (PAMAM) dendrimers decreases cytotoxicity while maintaining membrane permeability. Bioconjug. Chem., 2007, 18(6), 2054-2060.
[http://dx.doi.org/10.1021/bc0603889] [PMID: 17960872]
[13]
Organista-Mateos, U.; Pedro-Hernández, L.D.; Martínez-Klimova, E.; Cortez-Maya, S.; Ramírez-Ápan, T.; Martínez-García, M. Asymmetrical naproxen- conjugated den-drimer for targeted-drug delivery to human prostatic adenocarcinoma cancer cells. J. Pharm. Pharmacogn. Res., 2019, 2(3), 1-4.
[http://dx.doi.org/10.31038/JPPR.2019235]
[14]
D’Emanuele, A.; Jevprasesphant, R.; Penny, J.; Attwood, D. The use of a dendrimer-propranolol prodrug to bypass efflux transporters and enhance oral bioavailability. J. Control. Release, 2004, 95(3), 447-453.
[http://dx.doi.org/10.1016/j.jconrel.2003.12.006] [PMID: 15023456]
[15]
Wei, J.; Shi, J.; Zhang, J.; He, G.; Pan, J.; He, J.; Zhou, R.; Guo, L.; Ouyang, L. Design, synthesis and biological evaluation of enzymatically cleavable NSAIDs prodrugs derived from self-immolative dendritic scaffolds for the treatment of inflammatory diseases. Bioorg. Med. Chem., 2013, 21(14), 4192-4200.
[http://dx.doi.org/10.1016/j.bmc.2013.05.006] [PMID: 23719287]
[16]
Najlah, M.; Freeman, S.; Khoder, M.; Attwood, D.; D’Emanuele, A. In vitro evaluation of third generation PAMAM dendrimer conjugates. Molecules, 2017, 22(10), 1661.
[http://dx.doi.org/10.3390/molecules22101661] [PMID: 28976921]
[17]
Pedro-Hernández, L.D.; Ramirez-Ápan, T.; Martínez-García, M. Synthesis of bifunctional tris‐dendrimers conjugated with ibuprofen and naproxen. Chem. Select, 2022, 7(27)e202201335
[http://dx.doi.org/10.1002/slct.202201335]
[18]
Kaul, G.; Amiji, M. Long-circulating poly(ethylene glycol)-modified gelatin nanoparticles for intracellular delivery. Pharm. Res., 2002, 19(7), 1061-1067.
[http://dx.doi.org/10.1023/A:1016486910719] [PMID: 12180540]
[19]
Shen, X.; Liu, X.; Li, R.; Yun, P.; Li, C.; Su, F.; Li, S. Biocompatibility of filomicelles prepared from poly(ethylene glycol)-polylactide diblock copolymers as potential drug carrier. J. Biomater. Sci. Polym. Ed., 2017, 28(15), 1677-1694.
[http://dx.doi.org/10.1080/09205063.2017.1344383] [PMID: 28627288]
[20]
Caliceti, P.; Veronese, F.M. Pharmacokinetic and biodistribution properties of poly(ethylene glycol)–protein conjugates. Adv. Drug Deliv. Rev., 2003, 55(10), 1261-1277.
[http://dx.doi.org/10.1016/S0169-409X(03)00108-X] [PMID: 14499706]
[21]
Kingshott, P.; Wei, J.; Bagge-Ravn, D.; Gadegaard, N.; Gram, L. Covalent attachment of poly(ethylene glycol) to surfaces, critical for reducing bacterial adhesion. Langmuir, 2003, 19(17), 6912-6921.
[http://dx.doi.org/10.1021/la034032m]
[22]
Kesharwani, P.; Jain, K.; Jain, N.K. Dendrimer as nanocarrier for drug delivery. Prog. Polym. Sci., 2014, 39(2), 268-307.
[http://dx.doi.org/10.1016/j.progpolymsci.2013.07.005]
[23]
Aljubailah, A.; Alqahtani, S.M.S.; Al-Garni, T.S.; Saeed, W.S.; Semlali, A.; Aouak, T. Naproxen-loaded poly(2-hydroxyalkyl methacrylates): Preparation and drug release dynamics. Polymers, 2022, 14(3), 450.
[http://dx.doi.org/10.3390/polym14030450] [PMID: 35160440]
[24]
Kundaragi, N.G.; Asthana, S.; Reddy, J.; Lochan, R. Hepatic arterial communicating arcades – cases series and review of literature. Intervent. Med. Clinic. Imag., 2019, 2(1), 1-5.
[http://dx.doi.org/10.31038/IMCI.2019216]

Rights & Permissions Print Cite
Article Metrics
35
3
© 2024 Bentham Science Publishers | Privacy Policy