Functionalized calix[4]arenes as potential therapeutic agents

Abstract

Calixarenes, composed of phenolic units linked by methylene bridges at the 2,6-positions, represent a versatile class of macrocyclic compounds in supramolecular chemistry that can host small molecules or ions in their well-defined hydrophobic cavities. In recent years, it has been recognized that this class of compounds has the potential to serve as platform for the design of biological active compounds. Therefore, the calixarenes functionalized with different pharmacophoric groups have been synthesized as target structure by many researchers and were further evaluated for their biological activities. Owing to their promising biological activities such as antiviral, antibacterial, antifungal, and anticancer, the functionalized calixarenes are recently receiving increased attention from pharmaceutical/medicinal chemistry community. In this review, we summarize and discuss the synthetic approaches and the biological potential of functionalized calixarenes, mainly focusing on the selected recent studies for a comprehensive and target-oriented information, which could help in the design and synthesis of new therapeutic agents leading to the development of clinically viable drugs based on these macrocyles. K E Y W O R D Sbiological activity, calixarenes, cone conformation, functionalization, upper/lower rim/annulus

An Electron‐Rich Calix[4]arene‐Based Receptor with Unprecedented Binding Affinity for Nitric Oxide

“…Calixarenes derived from base‐catalyzed condensation of 4‐ tert ‐butylphenol/formaldehyde have found widespread application as building blocks for the design and synthesis of functional materials in host–guest chemistry . Such calixarenes exist as multiple conformers, affording further tailoring of their properties.…”

“…We find that 3/3 + C is ar emarkable receptor for NO + /NO, with unprecedented binding efficacy.T he availability of precise experimental structures of this calixarene derivative and its NO complex,o btained by X-ray crystallography,i sc ritically important both for developing novel functional NO biosensors, and understanding the role of stacked aromaticd onors in efficient NO binding, which may have relevance to biologicalN O transport.Calixarenes derived from base-catalyzedc ondensation of 4tert-butylphenol/formaldehyde have found widespread application as buildingb locks for the design and synthesis of functional materials in host-guest chemistry. [1][2][3][4][5][6][7] Such calixarenes exist as multiple conformers,a ffording further tailoring of their properties. It has been shown that, upon its activation via 1Àe À oxidation, the conformationally mobile p-tert-butylcalix[4]arene-OMe (1)b inds nitric oxide (NO) with nanomolar efficiency (K > 5 10 8 )l eading to the formation of the [1,N O] + complex.…”

“…Calixarenes derived from base-catalyzedc ondensation of 4tert-butylphenol/formaldehyde have found widespread application as buildingb locks for the design and synthesis of functional materials in host-guest chemistry. [1][2][3][4][5][6][7] Such calixarenes exist as multiple conformers,a ffording further tailoring of their properties. It has been shown that, upon its activation via 1Àe À oxidation, the conformationally mobile p-tert-butylcalix [4]arene-OMe (1)b inds nitric oxide (NO) with nanomolar efficiency (K > 5 10 8 )l eading to the formation of the [1,N O] + complex.…”

Macrocycles, the edge of drug‐likeness chemical space or Goldilocks zone?

“…The use of macrocycles as scaffolds is highlighted by Naseer and co‐workers with a review on therapeutic potential of calix[4]arenes. Calix[4]arenes are well known for their well‐defined central cavity and host–guest properties, but the potential of these structures as molecular scaffolds for biologically active molecules is less well appreciated.…”

Calix[4]arene‐Based Bis(Nitric Oxide) Complexes: Synthesis, Physical Properties, and Structural Characterization

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] Among the various molecular scaffolds that have been used for this purpose, one of the mostn otable is calix [4]arene, ac lass of macrocycles that has been widely employeda sb uildingb locks and molecular platforms in supramolecular chemistry. [11,[15][16][17][18][19][20][21][22][23][24][25][26] Calix [4]arenes are conformationally mobile moleculest hat have four conformers,t hat is, 1,3-alternate, 1,2-alternate, cone, and partial cone, with different cavity sizes. Therefore, calix [4]arenes have many potential applicationsi ns upramolecular host-guest chemistry and molecular sensing,s uch as the sensing of NO.…”