Assessment of the Toxicity of Calixarenes and a Metal-seamed Calixarene: a Chemical Pathway for Clinical Application

Overview

Journal Supramol Chem

Date 2019 Aug 3

PMID 31371909

Citations 5

Authors

Arnab Dawn

Xue Yao

Ying Yu

Jianxiong Jiang

Harshita Kumari

Affiliations

Soon will be listed here.

Abstract

Calixarenes are known to form host-guest complexes and supramolecular nanoassemblies with well-defined architectures. However, the use of these materials in conjunction with drug moieties is still under explored. One reason is the insuffcient biocompatibility studies. Our present study represents a systematic investigation of the cytotoxicity associated with -methylresorcin[4]arene, -methylpyrogallol[4]arene, p-phosphonated calix[8]arene and a metal-seamed calixarene-copper(II) complex, using human HEK293 and rat C6G cell lines and two different cell viability assays (MTT and CellTiter-Glo) to avoid species-biased results. All compounds showed low to moderate toxicity. The trend in the CC values indicated that the suppression of the coordination ability and the presence of phosphonate groups decrease the overall cytotoxicity of the compounds. The results of this study not only establish calixarenes and their immediate families as potential drug carriers and drug modifiers, but also reveal a pathway for fine-tuning their toxicological behaviour by appropriate chemical modification.

Citing Articles

PAHs removal by soil washing with thiacalix[4]arene tetrasulfonate.

Xing L, Meng G, Yang J, Xu M, Xu Y, Xie H Environ Sci Ecotechnol. 2024; 21:100422.

PMID: 38746775 PMC: 11091519. DOI: 10.1016/j.ese.2024.100422.

Investigating partitioning of free macrocycle bound guest into a model POPC lipid bilayer.

Kumari H, Eisenhart A, Pajoubpong J, Heinrich F, Beck T RSC Adv. 2022; 10(26):15148-15153.

PMID: 35495443 PMC: 9052308. DOI: 10.1039/d0ra02850a.

Targeting Colorectal Cancer Cells with a Functionalised Calix[4]arene Receptor: Biophysical Studies.

Danil de Namor A, Al Hakawati N, Farhat S Molecules. 2022; 27(2).

PMID: 35056825 PMC: 8779440. DOI: 10.3390/molecules27020510.

EP2 Antagonists (2011-2021): A Decade's Journey from Discovery to Therapeutics.

Sluter M, Hou R, Li L, Yasmen N, Yu Y, Liu J J Med Chem. 2021; 64(16):11816-11836.

PMID: 34352171 PMC: 8455147. DOI: 10.1021/acs.jmedchem.1c00816.

Role of Calixarene in Chemotherapy Delivery Strategies.

Basilotta R, Mannino D, Filippone A, Casili G, Prestifilippo A, Colarossi L Molecules. 2021; 26(13).

PMID: 34209495 PMC: 8272165. DOI: 10.3390/molecules26133963.

References

Berridge M, Herst P, Tan A . Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev. 2005; 11:127-52. DOI: 10.1016/S1387-2656(05)11004-7. View

Perret F, Lazar A, Coleman A . Biochemistry of the para-sulfonato-calix[n]arenes. Chem Commun (Camb). 2006; (23):2425-38. DOI: 10.1039/b600720c. View

Dings R, Chen X, Hellebrekers D, van Eijk L, Zhang Y, Hoye T . Design of nonpeptidic topomimetics of antiangiogenic proteins with antitumor activities. J Natl Cancer Inst. 2006; 98(13):932-6. DOI: 10.1093/jnci/djj247. View

Kowol C, Trondl R, Heffeter P, Arion V, Jakupec M, Roller A . Impact of metal coordination on cytotoxicity of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (triapine) and novel insights into terminal dimethylation. J Med Chem. 2009; 52(16):5032-43. DOI: 10.1021/jm900528d. View

Danylyuk O, Suwinska K . Solid-state interactions of calixarenes with biorelevant molecules. Chem Commun (Camb). 2009; (39):5799-813. DOI: 10.1039/b910331g. View

Jiang J, Ganesh T, Du Y, Thepchatri P, Rojas A, Lewis I . Neuroprotection by selective allosteric potentiators of the EP2 prostaglandin receptor. Proc Natl Acad Sci U S A. 2010; 107(5):2307-12. PMC: 2836658. DOI: 10.1073/pnas.0909310107. View

Uzunova V, Cullinane C, Brix K, Nau W, Day A . Toxicity of cucurbit[7]uril and cucurbit[8]uril: an exploratory in vitro and in vivo study. Org Biomol Chem. 2010; 8(9):2037-42. DOI: 10.1039/b925555a. View

Elidrisi I, Negin S, Bhatt P, Govender T, Kruger H, Gokel G . Pore formation in phospholipid bilayers by amphiphilic cavitands. Org Biomol Chem. 2011; 9(12):4498-506. DOI: 10.1039/c0ob01236j. View

Van Meerloo J, Kaspers G, Cloos J . Cell sensitivity assays: the MTT assay. Methods Mol Biol. 2011; 731:237-45. DOI: 10.1007/978-1-61779-080-5_20. View

10.

Perret F, Coleman A . Biochemistry of anionic calix[n]arenes. Chem Commun (Camb). 2011; 47(26):7303-19. DOI: 10.1039/c1cc11541c. View

11.

Martin A, Raston C . Multifunctional p-phosphonated calixarenes. Chem Commun (Camb). 2011; 47(35):9764-72. DOI: 10.1039/c1cc12048d. View

12.

Daglia M . Polyphenols as antimicrobial agents. Curr Opin Biotechnol. 2011; 23(2):174-81. DOI: 10.1016/j.copbio.2011.08.007. View

13.

Kumari H, Kline S, Schuster N, Atwood J . Solution structure of copper-seamed C-alkylpyrogallol[4]arene nanocapsules with varying chain lengths. Chem Commun (Camb). 2011; 47(45):12298-300. DOI: 10.1039/c1cc15615b. View

14.

Kumari H, Mossine A, Kline S, Dennis C, Fowler D, Teat S . Controlling the self-assembly of metal-seamed organic nanocapsules. Angew Chem Int Ed Engl. 2012; 51(6):1452-4. DOI: 10.1002/anie.201107182. View

15.

Kumari H, Kline S, Atwood J . Investigation of encapsulation of insulin biotemplate within C-methylresorcin[4]arenes. Chem Commun (Camb). 2012; 48(30):3599-601. DOI: 10.1039/c2cc18071e. View

16.

Jiang J, Dingledine R . Role of prostaglandin receptor EP2 in the regulations of cancer cell proliferation, invasion, and inflammation. J Pharmacol Exp Ther. 2012; 344(2):360-7. PMC: 3558819. DOI: 10.1124/jpet.112.200444. View

17.

Kumari H, Dennis C, Mossine A, Deakyne C, Atwood J . Magnetic differentiation of pyrogallol[4]arene tubular and capsular frameworks. J Am Chem Soc. 2013; 135(19):7110-3. DOI: 10.1021/ja402496x. View

18.

Gokel G, Negin S . Synthetic ion channels: from pores to biological applications. Acc Chem Res. 2013; 46(12):2824-33. DOI: 10.1021/ar400026x. View

19.

Geraci C, Consoli G, Granata G, Galante E, Palmigiano A, Pappalardo M . First self-adjuvant multicomponent potential vaccine candidates by tethering of four or eight MUC1 antigenic immunodominant PDTRP units on a calixarene platform: synthesis and biological evaluation. Bioconjug Chem. 2013; 24(10):1710-20. DOI: 10.1021/bc400242y. View

20.

Yeh Y, Saha K, Yan B, Miranda O, Yu X, Rotello V . The role of ligand coordination on the cytotoxicity of cationic quantum dots in HeLa cells. Nanoscale. 2013; 5(24):12140-12143. PMC: 3858971. DOI: 10.1039/c3nr04037b. View