Calixarenes as New Platforms for Drug Design

Abstract

Calixarenes, macrocyclic compounds of phenolic units linked by methylene groups at the 2,6-positions, present some of the requirements to serve as platforms for the design and synthesis of biological active compounds. They are also interesting host molecules for chemical biology study purposes. Their basic molecular scaffold has potential ability for molecule recognition; it is promptly synthesized in large amounts, and might be easily modified for maximizing molecular interactions toward relevant guest molecules. Calixarenes present well-defined conformational properties and cavities with molecular dimensions that enable to encapsulate guest drugs. Calixarenes have been shown to have antiviral, antibacterial, antifungal, and anticancer activities (including HIV as target). We provide here an overview of the use of calixarenes either as new chemical entity of distinct biological activities or as host for bioactive guest molecules. The importance of calixarenes for drugs development is discussed. The use of Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) techniques for the study of calixarenes as biological molecule hosts is also described.

Synthesis of a Series of Novel Tetra-tert-butylcalix[4]arene Linked to 1,2,4-Triazole and 1,3,4-Oxadiazole Derivatives

“…These compounds were synthesized according to the literature method 37,38 (Scheme 1). The synthesis of 5,11,17,23-tetra-tert-butyl-25,27-bis(3-bromopropoxy)-26,28-dihydroxycalix [4]arene (2) was carried out by the reaction of tetra-tert-butylcalix [4]arene (1) with 1,3-dibromo propane and K 2 CO 3 in acetonitrile according to the procedure reported in the literature 39 (Scheme 2). The existence of thiol-thione tautomerism is known for the compounds 3a-e and 5f-k and generally one forms is predominant.…”

“…Calixarene derivatives not only have been used in macromolecular chemistry, catalysis and separation techniques but they also have attracted much interest for their potential use in drug design and delivery. [1][2][3][4][5][6][7] Their controlled functionalization has allowed the use of these compounds in supramolecular chemistry as scaffolds for the construction of various receptors, carriers, and spatial organizers. Calix [4]arenes have been investigated for their biological proprieties; for example hydrophilic derivatives have shown interesting levels of activity against bacteria, cancerous cell, fungi, enveloped virus thrombosis, and fibrosis diseases.…”

Functionalized calix[4]arenes as potential therapeutic agents

“…One such macrocyclic scaffold is calixarene. [11][12][13][14][15][16][17][18][19][20] Calix [n]arenes are one of the most exciting synthetic macrocycles known to date besides cyclodextrins, crown ethers, cryptands, and cucurbiturils having diverse applications in supramolecular chemistry. [21][22][23] They can easily be synthesized by the reaction of p-tert-butyl phenol and formaldehyde in the presence of a base.…”

Influence of calixarene C-99 on contractile activity of rat large intestine smooth muscles

“…Одним із найбільш фармакологічно-перспектив-них класів сполук є каліксарени -макроциклічні сполуки, які одержують циклокон-денсацією пара-заміщених фенолів і формальдегіду. На сьогодні накопичено ве-ликий масив інформації щодо специфічної дії окремих каліксаренів як селективних рецепторів іонів і молекул, інгібіторів бактеріального росту, антимікозних і анти-тромботичних засобів тощо [23,10].…”