Calix[4]Resorcinarene Carboxybetaines and Carboxybetaine Esters: Synthesis, Investigation of In Vitro Toxicity, Anti-Platelet Effects, Anticoagulant Activity, and BSA Binding Affinities

Abstract

As a result of bright complexation properties, easy functionalization and the ability to self-organize in an aqueous solution, amphiphilic supramolecular macrocycles are being actively studied for their application in nanomedicine (drug delivery systems, therapeutic and theranostic agents, and others). In this regard, it is important to study their potential toxic effects. Here, the synthesis of amphiphilic calix[4]resorcinarene carboxybetaines and their esters and the study of a number of their microbiological properties are presented: cytotoxic effect on normal and tumor cells and effect on cellular and non-cellular components of blood (hemotoxicity, anti-platelet effect, and anticoagulant activity). Additionally, the interaction of macrocycles with bovine serum albumin as a model plasma protein is estimated by various methods (fluorescence spectroscopy, synchronous fluorescence spectroscopy, circular dichroic spectroscopy, and dynamic light scattering). The results demonstrate the low toxicity of the macrocycles, their anti-platelet effects at the level of acetylsalicylic acid, and weak anticoagulant activity. The study of BSA–macrocycle interactions demonstrates the dependence on macrocycle hydrophilic/hydrophobic group structure; in the case of carboxybetaines, the formation of complexes prevents self-aggregation of BSA molecules in solution. The present study demonstrates new data on potential drug delivery nanosystems based on amphiphilic calix[4]resorcinarenes for their cytotoxicity and effects on blood components.

Pillar[5]arene/albumin biosupramolecular systems for simultaneous native protein preservation and encapsulation of a water-soluble substrate

“…It is known that betaine macrocycle derivatives (sulfo-and carboxy-) of different nature are able to change the microenvironment of protein molecules by shifting the polarity of the medium and binding to them through a large number of noncovalent interactions (hydrogen bonds, van der Waals, hydrophobic forces, etc.). 46,47 In this regard, it was interesting to trace the changes in protein emission upon interaction with the synthesized decasubstituted pillar [5]arenes with carboxybetaine fragments.…”

Dual Brønsted acidic-basic function immobilized on the 3D mesoporous polycalix [4]resorcinarene: As a highly recyclable catalyst for the synthesis of spiro acenaphthylene/indene heterocycles

“…Calix [4]resorcinarene (C4RA) is one of the derivatives of C4A, made up of four resorcinol units connected by methylene bridges [ 56 , 57 ]. The substituent groups at the methylene bridges determine the conformers of C4RA, resulting in five stable isomers [ 56 , [58] , [59] , [60] , [61] , [62] ]. Modifying C4RA through various functional groups onto the eight hydroxyphenyl groups and aromatic rings provides a versatile platform for their multi-purpose use.…”