Generic placeholder image

Medicinal Chemistry

Author(s): Soumyajeet Paul, Ramaiah Selladurai Jeyaprakash, Aravinda Pai, Hillemane Venkatachalam and Bellur Srinivas Jayashree*

DOI: 10.2174/1573406419666230703114605

DownloadDownload PDF Flyer Cite As
Calixarenes and their Relevance in Anticancer Drug Development

Page: [939 - 945] Pages: 7

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Calixarenes have always captured the attention of several researchers. They have the ability to entrap multiple molecules and form inclusion complexes with drugs due to their unique structure. Due to this property, they are being widely used in the development of several classes of drugs, most notably anticancer drugs. This review attempted to summarize the potential applications of calixarenes and its derivatives in the development of anticancer drugs, with a focus on the delivery of drug classes such as DNA intercalators, taxanes, DNA alkylators, and topoisomerase inhibitors. Calixarene-based macromolecular chemistry could therefore have a high potential for overcoming the toxicity of cancer chemotherapy and achieving targeted drug delivery.

Keywords: Calixarenes, chemotherapy, inclusion complex, targeted drug delivery, macromolecular chemistry, anticancer drugs.

Graphical Abstract

[1]
David, G.C.; Lin, L-G. Calixarenes 12: The synthesis of functionalized calixarenes. Tetrahedron, 1986, 42(6), 1633-1640.
[http://dx.doi.org/10.1016/S1773-2247(04)50001-1]
[2]
Da Silva, E.; Lazar, A.N.; Coleman, A.W. Biopharmaceutical applications of calixarenes. J. Drug Deliv. Sci. Technol., 2004, 14(1), 3-20.
[http://dx.doi.org/10.1016/S1773-2247(04)50001-1]
[3]
Hussain, M.A.; Ashraf, M.U.; Muhammad, G.; Tahir, M.N.; Bukhari, S.N.A. Calixarene: A versatile material for drug design and applications. Curr. Pharm. Des., 2017, 23(16), 2377-2388.
[PMID: 27779081]
[4]
Shah, M.D. Calixarene: A new architecture in the analytical and pharmaceutical technology. J. Sci. Ind. Res., 2012, 71(1), 21-26.
[5]
Nimse, S.B.; Kim, T. Biological applications of functionalized calixarenes. Chem. Soc. Rev., 2013, 42(1), 366-386.
[http://dx.doi.org/10.1039/C2CS35233H] [PMID: 23032718]
[6]
Menger, F.M. Supramolecular chemistry and self-assembly. Proc. Natl. Acad. Sci. USA, 2002, 99(8), 4818-4822.
[http://dx.doi.org/10.1073/pnas.062524299] [PMID: 11959932]
[7]
Antesberger, J.; Cave, G.W.V.; Ferrarelli, M.C.; Heaven, M.W.; Raston, C.L.; Atwood, J.L. Solvent-free, direct synthesis of supramolecular nano-capsules. Chem. Commun., 2005, (7), 892-894.
[http://dx.doi.org/10.1039/b412251h] [PMID: 15700072]
[8]
Turro, N.J. From molecular chemistry to supramolecular chemistry to superdupermolecular chemistry. Controlling covalent bond formation through non-covalent and magnetic interactions. Chem. Commun., 2002, (20), 2279-2292.
[http://dx.doi.org/10.1039/b205552j] [PMID: 12430407]
[9]
Arduini, A.; Casnati, A. In: Harwood, L.M.; Moddy, C.J., Eds.; Macrocycle Synthesis; Oxford University Press: Oxford, 1996.
[10]
Pedersen, C.J. The discovery of crown ethers (Noble Lecture). Angew. Chem. Int. Ed. Engl., 1988, 27(8), 1021-1027.
[http://dx.doi.org/10.1002/anie.198810211]
[11]
Zhang, M.; Yan, X.; Huang, F.; Niu, Z.; Gibson, H.W. Stimuli-responsive host-guest systems based on the recognition of cryptands by organic guests. Acc. Chem. Res., 2014, 47(7), 1995-2005.
[http://dx.doi.org/10.1021/ar500046r] [PMID: 24804805]
[12]
Kurkov, S.V.; Loftsson, T. Cyclodextrins. Int. J. Pharm., 2013, 453(1), 167-180.
[http://dx.doi.org/10.1016/j.ijpharm.2012.06.055] [PMID: 22771733]
[13]
Giuliani, M.; Morbioli, I.; Sansone, F.; Casnati, A. Moulding calixarenes for biomacromolecule targeting. Chem. Commun., 2015, 51(75), 14140-14159.
[http://dx.doi.org/10.1039/C5CC05204A] [PMID: 26286064]
[14]
Schrader, T. Calixarene connection. Nat. Chem., 2012, 4(7), 519-520.
[http://dx.doi.org/10.1038/nchem.1386] [PMID: 22717431]
[15]
Yousaf, A.; Hamid, S.A.; Bunnori, N.M.; Ishola, A.A. Applications of calixarenes in cancer chemotherapy: Facts and perspectives. Drug Des. Devel. Ther., 2015, 9, 2831-2838.
[PMID: 26082613]
[16]
Lebrón, A.J.; López-López, M.; García-Calderón, C.B.; Rosado, I.V.; Balestra, F.R.; Huertas, P.; Rodik, R.V.; Kalchenko, V.I.; Rosado, I.V.; Bernal, E.; Moyá, M.L.; López-Cornejo, P.; Ostos, F.J. Multivalent calixarene-based liposomes as platforms for gene and drug delivery. Pharmaceutics, 2021, 13(8), 1250.
[17]
Deska, M.; Dondela, B.; Sliwa, W. Selected applications of calixarene derivatives. Arkivoc, 2015, 6, 393-416.
[http://dx.doi.org/10.3998/ark.5550190.p008.958]
[18]
Park, C.; Lee, I.H.; Lee, S.; Song, Y.; Rhue, M.; Kim, C. Cyclodextrin-covered organic nanotubes derived from self-assembly of dendrons and their supramolecular transformation. Proc. Natl. Acad. Sci. USA, 2006, 103(5), 1199-1203.
[http://dx.doi.org/10.1073/pnas.0505364103] [PMID: 16423900]
[19]
Rodríguez-Hernández, J.; Lecommandoux, S. Reversible inside-out micellization of pH-responsive and water-soluble vesicles based on polypeptide diblock copolymers. J. Am. Chem. Soc., 2005, 127(7), 2026-2027.
[http://dx.doi.org/10.1021/ja043920g] [PMID: 15713063]
[20]
Du, J.; Tang, Y.; Lewis, A.L.; Armes, S.P. pH-sensitive vesicles based on a biocompatible zwitterionic diblock copolymer. J. Am. Chem. Soc., 2005, 127(51), 17982-17983.
[http://dx.doi.org/10.1021/ja056514l] [PMID: 16366531]
[21]
Liu, X.; Jiang, M. Optical switching of self-assembly: Micellization and micelle-hollow-sphere transition of hydrogen-bonded polymers. Angew. Chem. Int. Ed., 2006, 45(23), 3846-3850.
[http://dx.doi.org/10.1002/anie.200504364] [PMID: 16646091]
[22]
Wang, K.; Guo, D.S.; Wang, X.; Liu, Y. Multistimuli responsive supramolecular vesicles based on the recognition of p-Sulfonatocalixarene and its controllable release of doxorubicin. ACS Nano, 2011, 5(4), 2880-2894.
[http://dx.doi.org/10.1021/nn1034873] [PMID: 21443257]
[23]
Qin, S.; Geng, Y.; Discher, D.E.; Yang, S. Temperature-controlled assembly and release from polymer vesicles of poly(ethylene oxide)-block- poly(N-isopropylacrylamide). Adv. Mater., 2006, 18(21), 2905-2909.
[http://dx.doi.org/10.1002/adma.200601019]
[24]
Napoli, A.; Valentini, M.; Tirelli, N.; Müller, M.; Hubbell, J.A. Oxidation-responsive polymeric vesicles. Nat. Mater., 2004, 3(3), 183-189.
[http://dx.doi.org/10.1038/nmat1081] [PMID: 14991021]
[25]
Kim, E.; Kim, D.; Jung, H.; Lee, J.; Paul, S.; Selvapalam, N.; Yang, Y.; Lim, N.; Park, C.G.; Kim, K. Facile, template-free synthesis of stimuli-responsive polymer nanocapsules for targeted drug delivery. Angew. Chem. Int. Ed., 2010, 49(26), 4405-4408.
[http://dx.doi.org/10.1002/anie.201000818] [PMID: 20468019]
[26]
Stone, M.M.; Franz, A.H.; Lebrilla, C.B. Non-covalent calixarene-amino acid complexes formed by MALDI-MS. J. Am. Soc. Mass Spectrom., 2002, 13(8), 964-974.
[http://dx.doi.org/10.1016/S1044-0305(02)00417-8] [PMID: 12216737]
[27]
Hu, X.; Pan, Z.; Wang, L.; Shi, X. The molecular recognition of tetra(p-t-butyl)tetrathiocalix[4]arene and its derivatives to heavy metal ions. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2003, 59(11), 2419-2423.
[http://dx.doi.org/10.1016/S1386-1425(02)00294-9] [PMID: 12963439]
[28]
Jin, Mei C.; Ainliah AA, S. A review on the determination heavy metals ions using calixarene-based electrochemical sensors. Arab. J. Chem., 2021, 14(9), 103303.
[http://dx.doi.org/10.1016/j.arabjc.2021.103303]
[29]
Dalgarno, S.J.; Raston, C.L. Capture of di-protonated[2,2,2] cryptand in the cavity of two p-sulfonated calixarenes as part of 2-D bi-layer lanthanide coordination polymers. Chem. Commun., 2002, 19, 2216-2217.
[http://dx.doi.org/10.1039/b207922b] [PMID: 12397985]
[30]
Shahgaldian, P.; Sciotti, M.A.; Pieles, U. Amino-substituted amphiphilic calixarenes: Self-assembly and interactions with DNA. Langmuir, 2008, 24(16), 8522-8526.
[http://dx.doi.org/10.1021/la801083h] [PMID: 18627190]
[31]
Kotch, F.W.; El-Kouedi, M.; Davis, J.T. Toward artificial ion channels: Self-assembled nanotubes from calix[4]arene-guanosine conjugate. Chem. Commun., 2000, 23, 2369-2370.
[32]
Dalgarno, S.J.; Warren, J.E.; Antesberger, J.; Glass, T.E.; Atwood, J.L. Large diameter non-covalent nanotubes based on the self-assembly of para-carboxylatocalix[4]arene. New J. Chem., 2007, 31(11), 1891-1894.
[http://dx.doi.org/10.1039/b712800b]
[33]
Arduini, A.; Ferdani, R.; Pochini, A.; Secchi, A.; Ugozzoli, F. Calix[6] arene as wheel for rotaxane synthesis. Angew. Chem. Int. Ed., 2000, 39(19), 3453-3456.
[http://dx.doi.org/10.1002/1521-3773(20001002)39:19<3453:AID-ANIE3453>3.0.CO;2-I]
[34]
Gaeta, C.; Vysotsky, M.O.; Bogdan, A.; Böhmer, V. Fourfold [2]rotaxanes based on calix[4]arenes. J. Am. Chem. Soc., 2005, 127(38), 13136-13137.
[http://dx.doi.org/10.1021/ja054184z] [PMID: 16173728]
[35]
Lankshear, M.D.; Evans, N.H.; Bayly, S.R.; Beer, P.D. Anion-templated calix[4]arene-based pseudorotaxanes and catenanes. Chemistry, 2007, 13(14), 3861-3870.
[http://dx.doi.org/10.1002/chem.200700041] [PMID: 17415740]
[36]
Beck, J.B.; Rowan, S.J. Multistimuli, multiresponsive metallo-supramolecular polymers. J. Am. Chem. Soc., 2003, 125(46), 13922-13923.
[http://dx.doi.org/10.1021/ja038521k] [PMID: 14611204]
[37]
Blohm, D.H.; Guiseppi-Elie, A. New developments in microarray technology. Curr. Opin. Biotechnol., 2001, 12(1), 41-47.
[http://dx.doi.org/10.1016/S0958-1669(00)00175-0] [PMID: 11167071]
[38]
Jain, K.K. Applications of nanobiotechnology in clinical diagnostics. Clin. Chem., 2007, 53(11), 2002-2009.
[http://dx.doi.org/10.1373/clinchem.2007.090795] [PMID: 17890442]
[39]
Anderson, K.S.; Ramachandran, N.; Wong, J.; Raphael, J.V.; Hainsworth, E.; Demirkan, G.; Cramer, D.; Aronzon, D.; Hodi, F.S.; Harris, L.; Logvinenko, T.; LaBaer, J. Application of protein microarrays for multiplexed detection of antibodies to tumor antigens in breast cancer. J. Proteome Res., 2008, 7(4), 1490-1499.
[http://dx.doi.org/10.1021/pr700804c] [PMID: 18311903]
[40]
Lueking, A.; Horn, M.; Eickhoff, H.; Büssow, K.; Lehrach, H.; Walter, G. Protein microarrays for gene expression and antibody screening. Anal. Biochem., 1999, 270(1), 103-111.
[http://dx.doi.org/10.1006/abio.1999.4063] [PMID: 10328771]
[41]
Jayashree, B.S.; Nigam, S.; Pai, A.; Patel, H.K.; Reddy, N.D.; Kumar, N.; Rao, C.M. Targets in anticancer research--A review. Indian J. Exp. Biol., 2015, 53(8), 489-507.
[PMID: 26349312]
[42]
Jayashree, B.S.; Nikhil, P.S.; Paul, S. Bioisosterism in drug discovery and development - An Overview. Med. Chem., 2022, 18(9), 915-925.
[http://dx.doi.org/10.2174/1573406418666220127124228] [PMID: 35086456]
[43]
Kopeckova, K.; Eckschlager, T.; Sirc, J.; Hobzova, R.; Plch, J.; Hrabeta, J.; Michalek, J. Nanodrugs used in cancer therapy. Biomed. Pap. Med. Fac. Univ., 2019, 163(2), 122-131.
[http://dx.doi.org/10.5507/bp.2019.010]
[44]
Chaturvedi, V.K.; Singh, A.; Singh, V.K.; Singh, M.P. Cancer nanotechnology: A new revolution for cancer diagnosis and therapy. Curr. Drug Metab., 2019, 20(6), 416-429.
[http://dx.doi.org/10.2174/1389200219666180918111528] [PMID: 30227814]
[45]
Iqbal, J.; Anwar, F.; Afridi, S. Targeted drug delivery systems and their therapeutic applications in cancer and immune pathological conditions. Infect. Disord. Drug Targets, 2017, 17(3), 149-159.
[PMID: 28595539]
[46]
Yilmaz, B.; Bayrac, A.T.; Bayrakci, M. Evaluation of anticancer activities of novel facile synthesized Calix[n]arene sulfonamide analogs. Appl. Biochem. Biotechnol., 2020, 190(4), 1484-1497.
[http://dx.doi.org/10.1007/s12010-019-03184-x] [PMID: 31782087]
[47]
Cherenok, S.; Vovk, A.; Muravyova, I.; Shivanyuk, A.; Kukhar, V.; Lipkowski, J.; Kalchenko, V. Calix[4]arene α-aminophosphonic acids: Asymmetric synthesis and enantioselective inhibition of an alkaline phosphatase. Org. Lett., 2006, 8(4), 549-552.
[http://dx.doi.org/10.1021/ol052469a] [PMID: 16468708]
[48]
Zhou, H.; Wang, D.; Baldini, L.; Ennis, E.; Jain, R.; Carie, A.; Sebti, S.M.; Hamilton, A.D. Structure–activity studies on a library of potent calix[4]arene-based PDGF antagonists that inhibit PDGF-stimulated PDGFR tyrosine phosphorylation. Org. Biomol. Chem., 2006, 4(12), 2376-2386.
[http://dx.doi.org/10.1039/B515483A] [PMID: 16763682]
[49]
Basilotta, R.; Mannino, D.; Filippone, A.; Casili, G.; Prestifilippo, A.; Colarossi, L.; Raciti, G.; Esposito, E.; Campolo, M. Role of calixarene in chemotherapy delivery strategies. Molecules, 2021, 26(13), 3963.
[http://dx.doi.org/10.3390/molecules26133963] [PMID: 34209495]
[50]
Baggetto, L.G.; Coleman, W.A.; Lazar, A.N.; Magnard, S.; Michaud, M.H. Calixarene derivatives as anticancer agent. US Patent 20100056482 A1, 2010.
[51]
Nasuhi Pur, F.; Dilmaghani, K.A. Calixplatin: Novel potential anticancer agent based on the platinum complex with functionalized calixarene. J. Coord. Chem., 2014, 67(3), 440-448.
[http://dx.doi.org/10.1080/00958972.2014.890718]
[52]
Kamada, R.; Yoshino, W.; Nomura, T.; Chuman, Y.; Imagawa, T.; Suzuki, T.; Sakaguchi, K. Enhancement of transcriptional activity of mutant p53 tumor suppressor protein through stabilization of tetramer formation by calix[6]arene derivatives. Bioorg. Med. Chem. Lett., 2010, 20(15), 4412-4415.
[http://dx.doi.org/10.1016/j.bmcl.2010.06.053] [PMID: 20605095]
[53]
Pelizzaro-Rocha, K.J.; de Jesus, M.B.; Ruela-de-Sousa, R.R.; Nakamura, C.V.; Reis, F.S.; de Fátima, A.; Ferreira-Halder, C.V. Calix[6]arene bypasses human pancreatic cancer aggressiveness: Downregulation of receptor tyrosine kinases and induction of cell death by reticulum stress and autophagy. Biochim. Biophys. Acta Mol. Cell Res., 2013, 1833(12), 2856-2865.
[http://dx.doi.org/10.1016/j.bbamcr.2013.07.010] [PMID: 23872419]
[54]
Songbo, M.; Lang, H.; Xinyong, C.; Bin, X.; Ping, Z.; Liang, S. Oxidative stress injury in doxorubicin-induced cardiotoxicity. Toxicol. Lett., 2019, 307, 41-48.
[http://dx.doi.org/10.1016/j.toxlet.2019.02.013] [PMID: 30817977]
[55]
Ostos, F.J.; Lebrón, J.A.; Moyá, M.L.; López-López, M.; Sánchez, A.; Clavero, A.; García-Calderón, C.B.; Rosado, I.V.; López-Cornejo, P. P-Sulfocalix[6]arene as nanocarrier for controlled delivery of doxorubicin. Chem. Asian J., 2017, 12(6), 679-689.
[http://dx.doi.org/10.1002/asia.201601713] [PMID: 28112869]
[56]
Retout, M.; Blond, P.; Jabin, I.; Bruylants, G. Ultrastable PEGylated calixarene-coated gold nanoparticles with a tunable bioconjugation density for biosensing applications. Bioconjug. Chem., 2021, 32(2), 290-300.
[http://dx.doi.org/10.1021/acs.bioconjchem.0c00669] [PMID: 33439626]
[57]
An, L.; Wang, J.; Liu, J.; Zhao, Z.; Song, Y. Design, preparation, and characterization of Novel Calix[4]arene bioactive carrier for antitumor drug delivery. Front Chem., 2019, 7, 732.
[http://dx.doi.org/10.3389/fchem.2019.00732] [PMID: 31788467]
[58]
Zhu, L.; Chen, L. Progress in research on paclitaxel and tumor immunotherapy. Cell. Mol. Biol. Lett., 2019, 24(1), 40.
[http://dx.doi.org/10.1186/s11658-019-0164-y] [PMID: 31223315]
[59]
Li, M.; Mao, L.; Chen, M.; Li, M.; Wang, K.; Mo, J. Characterization of an amphiphilic phosphonated calixarene carrier loaded with carboplatin and paclitaxel: A preliminary study to treat colon cancer in vitro and in vivo. Front. Bioeng. Biotechnol., 2019, 7, 238.
[http://dx.doi.org/10.3389/fbioe.2019.00238] [PMID: 31632958]
[60]
Zhao, Z.M.; Wang, Y.; Han, J.; Zhu, H.D.; An, L. Preparation and characterization of amphiphilic calixarene nanoparticles as delivery carriers for paclitaxel. Chem. Pharm. Bull., 2015, 63(3), 180-186.
[http://dx.doi.org/10.1248/cpb.c14-00699] [PMID: 25757488]
[61]
Mo, J.; Eggers, P.K.; Yuan, Z.; Raston, C.L.; Lim, L.Y. Paclitaxel-loaded phosphonated calixarene nanovesicles as a modular drug delivery platform. Sci. Rep., 2016, 6(1), 23489.
[http://dx.doi.org/10.1038/srep23489] [PMID: 27009430]
[62]
Raval, J.; Trivedi, R.; Prajapati, P. Preparation, characterization, and in-vitro assessment of calixarene nanovesicles: A supramolecular based nano-carrier for paclitaxel drug delivery. Pharm. Chem. J., 2021, 55(6), 570-579.
[http://dx.doi.org/10.1007/s11094-021-02461-6]
[63]
Weeden, C.; Hartlieb, K.J.; Lim, L.Y. Preparation and physicochemical characterization of a novel paclitaxel-loaded amphiphilic aminocalixarene nanoparticle platform for anticancer chemotherapy. J. Pharm. Pharmacol., 2012, 64(10), 1403-1411.
[http://dx.doi.org/10.1111/j.2042-7158.2012.01518.x] [PMID: 22943171]
[64]
Ho, G.Y.; Woodward, N.; Coward, J.I.G. Cisplatin versus carboplatin: Comparative review of therapeutic management in solid malignancies. Crit. Rev. Oncol. Hematol., 2016, 102, 37-46.
[http://dx.doi.org/10.1016/j.critrevonc.2016.03.014] [PMID: 27105947]
[65]
Mo, J.; Wang, L.; Huang, X.; Lu, B.; Zou, C.; Wei, L.; Chu, J.; Eggers, P.K.; Chen, S.; Raston, C.L.; Wu, J.; Lim, L.Y.; Zhao, W. Multifunctional nanoparticles for co-delivery of paclitaxel and carboplatin against ovarian cancer by inactivating the JMJD3-HER2 axis. Nanoscale, 2017, 9(35), 13142-13152.
[http://dx.doi.org/10.1039/C7NR04473A] [PMID: 28849826]
[66]
Tourell, M.C.; Shokoohmand, A.; Landgraf, M.; Holzapfel, N.P.; Poh, P.S.P.; Loessner, D.; Momot, K.I. The distribution of the apparent diffusion coefficient as an indicator of the response to chemotherapeutics in ovarian tumour xenografts. Sci. Rep., 2017, 7(1), 42905.
[http://dx.doi.org/10.1038/srep42905] [PMID: 28220831]
[67]
Renziehausen, A.; Tsiailanis, A.D.; Perryman, R.; Stylos, E.K.; Chatzigiannis, C.; O’Neill, K.; Crook, T.; Tzakos, A.G.; Syed, N. Encapsulation of temozolomide in a calixarene nanocapsule improves its stability and enhances its therapeutic efficacy against glioblastoma. Mol. Cancer Ther., 2019, 18(9), 1497-1505.
[http://dx.doi.org/10.1158/1535-7163.MCT-18-1250] [PMID: 31213505]
[68]
Zhang, J.; Stevens, M.F.; Bradshaw, T.D. Temozolomide: Mechanisms of action, repair and resistance. Curr. Mol. Pharmacol., 2012, 5(1), 102-114.
[http://dx.doi.org/10.2174/1874467211205010102] [PMID: 22122467]
[69]
Beldner, M.A.; Sherman, C.A.; Green, M.R.; Garrett-Mayer, E.; Chaudhary, U.; Meyer, M.L.; Kraft, A.S.; Montero, A.J. Phase I dose escalation study of vinorelbine and topotecan combination chemotherapy in patients with recurrent lung cancer. BMC Cancer, 2007, 7(1), 231.
[http://dx.doi.org/10.1186/1471-2407-7-231] [PMID: 18096059]
[70]
Bhal, S.K.; Kassam, K.; Peirson, I.G.; Pearl, G.M. The Rule of Five revisited: Applying log D in place of log P in drug-likeness filters. Mol. Pharm., 2007, 4(4), 556-560.
[http://dx.doi.org/10.1021/mp0700209] [PMID: 17530776]