Assessment of the in vitro toxicity of calixarenes and a metal-seamed calixarene: a chemical pathway for clinical application

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 in vitro investigation of the cytotoxicity associated with Cmethylresorcin[4]arene, C-methylpyrogallol[4]arene, p-phosphonated calix[8]arene and a metalseamed 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 50 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.

EP2 Antagonists (2011–2021): A Decade’s Journey from Discovery to Therapeutics

“…The recently solved cryo-EM structures of the human EP2 receptor and G s protein complex are expected to play some fundamental roles in rational designs to develop the next-generation EP2 antagonists with further improved pharmacokinetic and pharmacodynamic properties for clinical applications (Figure ). In addition, the use of nanoparticles encapsulated by macrocycle-based compounds such as calixarenes for the controlled release of these potential therapeutic agents might also help in targeted therapy …”

Role of Calixarene in Chemotherapy Delivery Strategies

“…In fact, the calixarenes, due to the presence of different phenolic units within their structure, can be considered cyclic polyphenols [ 28 ]. These are secondary metabolites, extensively studied for their beneficial effects on human health, especially as antioxidants, antiallergic, anti-inflammatory, antitumor, antihypertensive and antimicrobial agents and their uses in biomaterial engineering [ 29 ]. The compound is called calix [n] arene, where n is the number of phenolic units present in the macrocyclic unit [ 30 ].…”

“…Today, the versatility of the chemical and structural aspects of calixarene has prompted researchers to explore new fields of application. These macrocyclic nano-capsules linked to metals have shown relevant action in biomedical applications, and in particular in imaging and drug administration [ 29 ]. Furthermore, it has been demonstrated that a nanohydrogel constructed from a calix [4] arene macrocycle can be used as a curcumin release vehicle.…”

Investigating partitioning of freeversusmacrocycle bound guest into a model POPC lipid bilayer

“…Our recent rat and human cell toxicology study on calix [8]-PO 3 H 2 revealed its non-toxic behaviour that renders it as a useful biomedical macrocycle for potential application as a nanocarrier. 25 avobenzone 26 was chosen for three reasons: (a) water solubility of the macrocycle; (b) large internal cavity and upper rim Hbonding functionality of the host and (c) non-toxic behaviour towards rat and human cell lines-. 25 Avobenzone (1-(4-methoxyphenyl)-3-(4-tertbutylphenyl)propane-1,3-dione) also known as Parsol 1789 is a broadspectrum sunscreen agent.…”

“…25 avobenzone 26 was chosen for three reasons: (a) water solubility of the macrocycle; (b) large internal cavity and upper rim Hbonding functionality of the host and (c) non-toxic behaviour towards rat and human cell lines-. 25 Avobenzone (1-(4-methoxyphenyl)-3-(4-tertbutylphenyl)propane-1,3-dione) also known as Parsol 1789 is a broadspectrum sunscreen agent. Its ability to absorb both UVA and UVB radiations makes it one of the most useful sunscreen agents that prevents photodamage of skin.…”