Conformationally Locked Calixarene-Based Histone Deacetylase Inhibitors

Abstract

Alkyl- and arylamidocalix[4]arene derivatives 1-11 have been designed and theoretically evaluated by docking studies as potential histone deacetylase inhibitors (HDACi). On the basis of the trimodal distribution of the calculated inhibition constants (K(i)), five alkyl- or arylamido derivatives (3, 7, 8, 9, and 11) were synthesized and tested. A qualitative accordance between the experimental results and the theoretical predictions was obtained, confirming that appropriately substituted arylamidocalix[4]arenes are active HDACi.

Recognition of exterior protein surfaces using artificial ligands based on calixarenes, crown ethers, and tetraphenylporphyrins

“…These calix [8]arene derivatives acted as indirect inhibitors through an antagonistic effect on the proteoglycan heparin, and direct competitive inhibitors of tryptase. Neri and co-workers developed calixarene derivatives that functioned as inhibitors for transglutaminase and histone deacetylase [45,46]. A series of N-linked tetrakis(tetrapeptide)calix [4]arene diversomers were synthesized for complexation with transglutaminase, and derivatives bearing a Gly-Phe-Gly-Tyr tetrapeptide exhibited the most effective inhibition.…”

“…Fig. 4 Molecular structures of glycocalixarenes [46] Liquid-liquid extraction of proteins using calixarenes A p-tert-octylcalix [6]arene carboxylic acid derivative ( Fig. 6) was found to extract proteins [66,67].…”

Molecular dynamics approach for capturing calixarenes--proteins interactions: the case of cytochrome c

“…Some are adapted to a daily routine use 28 while other rely on more advanced methods 29 , potentially bridged to MD simulations 30,31 . Successful docking approaches have been reported for small size calixarenes, such as calix- [4]-arenes [32][33][34] , in the context of design of drug carriers 35 , transport phenomena 36 or protein inhibitors 32,33 . Yet larger calixarenes prone to a higher flexibility may need the use of MD simulations, as recognized since the seminal paper by Gutsche and coworkers 37 .…”

Highly functionalized calix[4]arenesviamulticomponent reactions: synthesis and recognition properties

“…[8][9][10] The possibility of divers functionalization at lower and/or upper rim as well as unique conformational properties have made calix [4]arenes versatile templates to design outstanding supramolecular structures with several binding sites in an array complementary to a potential guest. [11][12][13] The molecular hosts based on calix [4]arene scaffold have been employed in many applications, 14,15 such as chemical sensing, [16][17][18] drug and gen delivery, [19][20][21][22] enzyme mimicking, 23,24 stationary phase, [25][26][27] extractants, 28,29 enzyme inhibitors, [30][31][32] catalysts [33][34][35] and etc.…”