Login Register Cart 0
Generic placeholder image

Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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

Anticancer Activity of 3,5-Bis(dodecyloxy)Benzoate-PAMAM Conjugates with Indomethacin or Mefenamic Acid

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

Volume 19, Issue 5, 2023

Published on: 19 January, 2023

Page: [460 - 467] Pages: 8

DOI: 10.2174/1573406419666221226095440

Price: $65

conference banner
Abstract

Background: The synthesis of conjugates with nonsteroidal anti-inflammatory drugs could improve their activity with less toxicity and these compounds could be used for the treatment of cancer.

Objective: The aim of the present investigation was the synthesis of 3,5-bis(dodecyloxy)benzoate - PAMAM conjugates with indomethacin and mefenamic acid to examine their anticancer activity.

Methods: The anticancer activity was studied of the conjugates against six human cancer cells U- 251, PC-3, K-562, HCT-15, MCF-7, SKLU-1, and the COS-7 (as a control) cell lines. The conjugates with indomethacin and mefenamic acid were characterized by 1H, 13C NMR one- and twodimension spectroscopy.

Results: All the conjugates synthetized with indomethacin or mefenamic acid showed anticancer activity against all the human cancer cell lines. The first generation of indomethacin conjugates showed better activity against the PC-3 (human prostatic adenocarcinoma) cell line than the second generation. But the second generation with indomethacin showed better activity against PC-3 than the first generation. The second-generation conjugate with mefenamic acid had strong selectivity to PC-3 cells with an IC50 value of 10.23 ± 1.2 μM in vitro.

Conclusion: In the paper, we report the synthesis and spectroscopic analyses of new indomethacin or mefenamic acid conjugates. The overall results showed that the conjugate of the second generation with mefenamic acid could be a potential nanocarrier for human prostatic adenocarcinoma cancer treatment, our research will be continued.

« Previous Next »
Graphical Abstract

[1]
Chauhan, A.S.; Jain, N.K.; Diwan, P.V.; Khopade, A.J. Solubility enhancement of indomethacin with poly(amidoamine) dendrimers and targeting to inflammatory regions of arthritic rats. J. Drug Target., 2004, 12(9-10), 575-583.
[http://dx.doi.org/10.1080/10611860400010655] [PMID: 15621683]
[2]
Smith, W.L.; DeWitt, D.L.; Garavito, R.M. Cyclooxygenases: Structural, cellular, and molecular biology. Annu. Rev. Biochem., 2000, 69(1), 145-182.
[http://dx.doi.org/10.1146/annurev.biochem.69.1.145] [PMID: 10966456]
[3]
Virchov, R. Cellular Pathology as Based Upon Physiological and Pathological Histology; J. B. Lippincott: Philadelphia, PA, USA, 1863.
[http://dx.doi.org/10.5962/bhl.title.32770]
[4]
Harris, R.E.; Chlebowski, R.T.; Jackson, R.D.; Frid, D.J.; Ascenseo, J.L.; Anderson, G.; Loar, A.; Rodabough, R.J.; White, E.; McTiernan, A. Breast cancer and nonsteroidal anti-inflammatory drugs: Prospective results from the Women’s health initiative. Cancer Res., 2003, 63(18), 6096-6101.
[PMID: 14522941]
[5]
Kim, S.; Shore, D.L.; Wilson, L.E.; Sanniez, E.I.; Kim, J.H.; Taylor, J.A.; Sandler, D.P. Lifetime use of nonsteroidal anti-inflammatory drugs and breast cancer risk: Results from a prospective study of women with a sister with breast cancer. BMC Cancer, 2015, 15(1), 960.
[http://dx.doi.org/10.1186/s12885-015-1979-1] [PMID: 26673874]
[6]
Dierssen-Sotos, T.; Gómez-Acebo, I.; de Pedro, M.; Pérez-Gómez, B.; Servitja, S.; Moreno, V.; Amiano, P.; Fernandez-Villa, T.; Barricarte, A.; Tardon, A.; Diaz-Santos, M.; Peiro-Perez, R.; Marcos-Gragera, R.; Lope, V.; Gracia-Lavedan, E.; Alonso, M.H.; Michelena-Echeveste, M.J.; Garcia-Palomo, A.; Guevara, M.; Castaño-Vinyals, G.; Aragonés, N.; Kogevinas, M.; Pollán, M.; Llorca, J. Use of non-steroidal anti-inflammatory drugs and risk of breast cancer: The Spanish Multi-Case-control (MCC) study. BMC Cancer, 2016, 16(1), 660.
[http://dx.doi.org/10.1186/s12885-016-2692-4] [PMID: 27542890]
[7]
Vidal, A.C.; Howard, L.E.; Moreira, D.M.; Castro-Santamaria, R.; Andriole, G.L.; Freedland, S.J. Aspirin, NSAIDs, and risk of prostate cancer: Results from the REDUCE study. Clin. Cancer Res., 2015, 21(4), 756-762.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-2235] [PMID: 25520389]
[8]
Doat, S.; Cénée, S.; Trétarre, B.; Rebillard, X.; Lamy, P.J.; Bringer, J.P.; Iborra, F.; Murez, T.; Sanchez, M.; Menegaux, F. Nonsteroidal anti-inflammatory drugs (NSAIDs) and prostate cancer risk: Results from the EPICAP study. Cancer Med., 2017, 6(10), 2461-2470.
[http://dx.doi.org/10.1002/cam4.1186] [PMID: 28941222]
[9]
Ruder, E.H.; Laiyemo, A.O.; Graubard, B.I.; Hollenbeck, A.R.; Schatzkin, A.; Cross, A.J. Non-steroidal anti-inflammatory drugs and colorectal cancer risk in a large, prospective cohort. Am. J. Gastroenterol., 2011, 106(7), 1340-1350.
[http://dx.doi.org/10.1038/ajg.2011.38] [PMID: 21407185]
[10]
Friis, S.; Riis, A.H.; Erichsen, R.; Baron, J.A.; Sørensen, H.T. Low-dose aspirin or nonsteroidal anti-inflammatory drug use and colorectal cancer risk. Ann. Intern. Med., 2015, 163(5), 347-355.
[http://dx.doi.org/10.7326/M15-0039] [PMID: 26302241]
[11]
Trabert, B.; Ness, R.B.; Lo-Ciganic, W.H.; Murphy, M.A.; Goode, E.L.; Poole, E.M.; Brinton, L.A.; Webb, P.M.; Nagle, C.M.; Jordan, S.J.; Risch, H.A.; Rossing, M.A.; Doherty, J.A.; Goodman, M.T.; Lurie, G.; Kjaer, S.K.; Hogdall, E.; Jensen, A.; Cramer, D.W.; Terry, K.L.; Vitonis, A.; Bandera, E.V.; Olson, S.; King, M.G.; Chandran, U.; Anton-Culver, H.; Ziogas, A.; Menon, U.; Gayther, S.A.; Ramus, S.J.; Gentry-Maharaj, A.; Wu, A.H.; Pearce, C.L.; Pike, M.C.; Berchuck, A.; Schildkraut, J.M.; Wentzensen, N. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: A pooled analysis in the ovarian cancer association consortium. J. Natl. Cancer Inst., 2014, 106(2), djt431.
[http://dx.doi.org/10.1093/jnci/djt431] [PMID: 24503200]
[12]
Shi, J.; Leng, W.; Zhao, L.; Xu, C.; Wang, J.; Chen, X.; Wang, Y.; Peng, X. Nonsteroidal anti-inflammatory drugs using and risk of head and neck cancer: A dose-response meta analysis of prospective cohort studies. Oncotarget, 2017, 8(58), 99066-99074.
[http://dx.doi.org/10.18632/oncotarget.21524] [PMID: 29228752]
[13]
Ahmadi, A. Synthesis and anti-inflammatory evaluation of novel thiadiazol derivatives of Mefenamic acid. Bull. Chem. Soc. Ethiop., 2017, 31(1), 171-175.
[http://dx.doi.org/10.4314/bcse.v31i1.15]
[14]
Bundgaard, H. (C) Means to enhance penetration. Adv. Drug Deliv. Rev., 1992, 8(1), 1-38.
[http://dx.doi.org/10.1016/0169-409X(92)90014-H]
[15]
Wang, H.M.; Zhang, G.Y. Indomethacin suppresses growth of colon cancer via inhibition of angiogenesis in vivo. World J. Gastroenterol., 2005, 11(3), 340-343.
[http://dx.doi.org/10.3748/wjg.v11.i3.340] [PMID: 15637740]
[16]
Jukić, M.K.; Luetić, A.T.; Skudar-Lukinović, V.; Andreis, I. The antimetastatic effect of macrophages restored by indomethacin: Concomitant tumor immunity model. Coll. Antropol., 2010, 34(3), 899-904.
[PMID: 20977080]
[17]
Brunelli, C.; Amici, C.; Angelini, M.; Fracassi, C.; Belardo, G.; Santoro, M.G. The non-steroidal anti-inflammatory drug indomethacin activates the eIF2α kinase PKR, causing a translational block in human colorectal cancer cells. Biochem. J., 2012, 443(2), 379-386.
[http://dx.doi.org/10.1042/BJ20111236] [PMID: 22268531]
[18]
Hojka-Osinska, A.; Ziolo, E.; Rapak, A. Combined treatment with fenretinide and indomethacin induces AIF-mediated, non-classical cell death in human acute T-cell leukemia Jurkat cells. Biochem. Biophys. Res. Commun., 2012, 419(3), 590-595.
[http://dx.doi.org/10.1016/j.bbrc.2012.02.092] [PMID: 22387538]
[19]
Waddell, W.R.; Gerner, R.E. Indomethacin and ascorbate inhibit desmoid tumors. J. Surg. Oncol., 1980, 15(1), 85-90.
[http://dx.doi.org/10.1002/jso.2930150113] [PMID: 7421272]
[20]
Sabah, A.A.; Al-Rawi, M.S.; Tomma, J.H. Study the toxicity and anticancer activity of some new amic acid and their derivatives of mefenamic acid. Indian J. Forensic Med. Toxicol, 2020, 14, 642-648.
[http://dx.doi.org/10.37506/v14/i1/2020/ijfmt/192974]
[21]
Kovala-Demertzi, D.; Hadjipavlou-Litina, D.; Staninska, M.; Primikiri, A.; Kotoglou, C.; Demertzis, M.A. Anti-oxidant, in vitro, in vivo anti-inflammatory activity and antiproliferative activity of mefenamic acid and its metal complexes with manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II). J. Enzyme Inhib. Med. Chem., 2009, 24(3), 742-752.
[http://dx.doi.org/10.1080/14756360802361589] [PMID: 18720191]
[22]
Shiiba, M.; Yamagami, H.; Yamamoto, A.; Minakawa, Y.; Okamoto, A.; Kasamatsu, A.; Sakamoto, Y.; Uzawa, K.; Takiguchi, Y.; Tanzawa, H. Mefenamic acid enhances anticancer drug sensitivity via inhibition of aldo-keto reductase 1C enzyme activity. Oncol. Rep., 2017, 37(4), 2025-2032.
[http://dx.doi.org/10.3892/or.2017.5480] [PMID: 28259989]
[23]
Čeponytė, U.; Paškevičiūtė, M.; Petrikaitė, V. Comparison of NSAIDs activity in COX‐2 expressing and non‐expressing 2D and 3D pancreatic cancer cell cultures. Cancer Manag. Res., 2018, 10, 1543-1551. http://dx.doi.org/10.2147/CMAR.S163747
[24]
Pedro-Hernández, L.; 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]
[25]
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.
[26]
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 calix[4]arene conjugates. Med. Chem., 2020, 16(7), 984-990.
[http://dx.doi.org/10.2174/1573406415666190826162339] [PMID: 31448714]
[27]
Organista-Mateos, U.; Pedro-Hernández, L.D.; Martínez-Klimova, E. Asymmetrical naproxen- conjugated dendrimer for targeted-drug delivery to human prostatic adenocarcinoma cancer cells. J. Pharm. Pharmacogn. Res., 2019, 2, 1-4.
[28]
Medina-Rojas, J.C.; Castillo-Rodríguez, I.O.; Martínez-Klimova, E.; Ramírez-Ápan, T.; Hernández-Ortega, S.; Martínez-García, M. Synthesis of flutamide-conjugates. Bioorg. Med. Chem. Lett., 2020, 30(21), 127507.
[http://dx.doi.org/10.1016/j.bmcl.2020.127507] [PMID: 32866675]
[29]
Yang, Y.; Wang, J.C.; Zhang, X.; Lu, W.L.; Zhang, Q. A novel mixed micelle gel with thermoesensitive property for the local delivery of docetaxel. J. Control. Release, 2009, 135, 175-182.
[http://dx.doi.org/10.1016/j.jconrel.2009.01.007]
[30]
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]
[31]
Mintzer, M.A.; Grinstaff, M.W. Biomedical applications of dendrimers: A tutorial. Chem. Soc. Rev., 2011, 40(1), 173-190.
[http://dx.doi.org/10.1039/B901839P] [PMID: 20877875]
[32]
Kesharwani, P.; Iyer, A.K. Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery. Drug Discov. Today, 2015, 20(5), 536-547.
[http://dx.doi.org/10.1016/j.drudis.2014.12.012] [PMID: 25555748]
[33]
Kannan, R.M.; Nance, E.; Kannan, S.; Tomalia, D.A. Emerging concepts in dendrimer-based nanomedicine: From design principles to clinical applications. J. Intern. Med., 2014, 276(6), 579-617.
[http://dx.doi.org/10.1111/joim.12280] [PMID: 24995512]
[34]
Wolinsky, J.; Grinstaff, M. Therapeutic and diagnostic applications of dendrimers for cancer treatment. Adv. Drug Deliv. Rev., 2008, 60(9), 1037-1055.
[http://dx.doi.org/10.1016/j.addr.2008.02.012] [PMID: 18448187]
[35]
Namazi, H.; Adeli, M. Dendrimers of citric acid and poly (ethylene glycol) as the new drug-delivery agents. Biomaterials, 2005, 26(10), 1175-1183.
[http://dx.doi.org/10.1016/j.biomaterials.2004.04.014] [PMID: 15451637]
[36]
Okda, T. Abd-Εlghaffar, S.; Katary, M.; Abd-αlhaseeb, M. Chemopreventive and anticancer activities of indomethacin and vitamin D combination on colorectal cancer induced by 1,2 dimethylhydrazine in rats. Biomed. Rep., 2020, 14(2), 27.
[http://dx.doi.org/10.3892/br.2020.1403] [PMID: 33408861]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy