Click synthesis of novel dendronized curcumin and analogs. Strengthening of physicochemical properties toward biological applications

Abstract

Curcumin and its analogs, chalcones, and C5-monocarbonyl are molecules of great therapeutic potential, but their poor stability and hydrophobicity have hampered their extensive use in clinical trials. Therefore, significant efforts...

Click synthesis of dendronized malonates for the preparation of amphiphilic dendro[60]fullerenes

“…The deprotection of dendronized methanofullerenes 21–24 was attempted using DOWEX-H+ in methanol at 60 °C for 1 hour, as previously reported. 48 However, only trace amounts of malonoester 25 and 26 (Fig. 5) were obtained, and malonamides 27 and 28 were not obtained under these reaction conditions (the starting material was consumed, none of the products corresponded to the desired derivatives).…”

“…44,45 These dendrons have used to enhance the aqueous solubility of curcumin by ester linkage 46,47 or by click chemistry. 48 Based on previous reports, we stated that dendronized malonic acid derivatives could enhance the aqueous solubility of fullerene C 60 by means of an amphiphilic system. On the other hand, the important hydrophobic moiety in C 60 remains accessible for protein interactions.…”

“…50 In this study, we developed the synthesis of first and second generation dendrons with azide group as focal point, as earlier reported methodologies (Scheme 1). 47,48 Firstly, the acetonides 2 and 4 were synthesized by the reaction of the corresponding polyalcohol 1 and 3 with 2,2-dimethoxypropane catalyzed with p-toluensulfonic acid. Then, the remaining hydroxyl of acetonide 4 was activated as a tosylate for its nucleophilic displacement with azide anion via S N 2 process, giving the first-generation dendron 6.…”

“…44,45 These dendrons have used to enhance the aqueous solubility of curcumin by ester linkage 46,47 or by click chemistry. 48…”

Versátil como ninguna, la química clic y su trascendencia en áreas diversas: de la ciencia de materiales a la investigación farmacéutica

“…Tomando ventaja de la reacción clic CuAAC, recientemente reportamos una estrategia sintética para fortalecer propiedades como la solubilidad acuosa y la estabilidad de la curcumina, y algunos análogos de interés biológico (Figura 5) [25]. Mediante la reacción clic entre sustituyentes altamente ramificados llamados dendrones, en este caso de poliéster, previamente funcionalizados con grupos azida, y la curcumina y análogos modificados con grupos alquino, logramos obtener conjugados que exhibieron una mejor solubilidad acuosa y estabilidad.…”