title: A two-step synthetic strategy to obtain a water-soluble derivative of curcumin with improved antioxidant capacity and in vitro cytotoxicity in C6 glioma cells.
abstract: A novel water-soluble derivative of curcumin (Cur-[G-2]-OH) was designed and synthesized from accessible raw materials in only two steps with an overall yield of 80%. The modification of curcumin phenol groups with second-generation polyester dendrons (dendronization) as a strategy to achieve an optimal hydrophilic/hydrophobic balance allows the complete water solubilization of the new curcumin derivative (5mg/ml) at room temperature. The therapeutic potential of Cur-[G-2]-OH was investigated in terms of antioxidant capacity, intracellular uptake and cytotoxicity in both rat glioblastoma cells and normal human dermal fibroblasts. Although the phenolic groups of curcumin were locked by dendronization, Cur-[G-2]-OH exhibited antioxidant capacity in water that was even higher than curcumin in dimethylsulfoxide (DMSO). This compound showed a steady cellular uptake contrasted with curcumin, which has a saturation capture at high concentrations. Combined with improved stability, this property seems to allow the intracellular accumulation of Cur-[G-2]-OH. Furthermore, the new compound exhibited increased cytotoxicity in rat C6 glioma cells in a time- and concentration-dependent manner, whereas in normal human fibroblasts, its IC50value was >600μM versus the IC50of curcumin found between 100 and 200μM. Surprisingly, Cur-[G-2]-OH drives cell death of C6 cells by a different mechanism of apoptosis triggered by curcumin. Together, these results suggest that curcumin dendronization could promote molecular and cellular mechanisms that are different from those induced by curcumin, presumably due to structural factors and not only for improved water solubility.
authors.affiliation: Instituto de Investigaciones en Materiales, Laboratorio de Materiales Funcionales Orgánicos, Universidad Nacional Autónoma de México, C.P. 70-360, CU, Coyoacán, México D.F. 04510, Mexico.
authors.forename: José M
authors.initials: JM
authors.lastname: Landeros
authors.affiliation: Instituto de Investigaciones en Materiales, Laboratorio de Materiales Funcionales Orgánicos, Universidad Nacional Autónoma de México, C.P. 70-360, CU, Coyoacán, México D.F. 04510, Mexico.
authors.forename: Fernando
authors.initials: F
authors.lastname: Belmont-Bernal
authors.affiliation: Instituto Nacional de Neurología y Neurocirugía, Laboratorio de Aminoácidos Excitadores, Insurgentes Sur 3877, Col. La Fama, México, D.F. C.P. 14-269, Mexico.
authors.forename: Alma Teresa
authors.initials: AT
authors.lastname: Pérez-González
authors.affiliation: Instituto Nacional de Neurología y Neurocirugía, Laboratorio de Aminoácidos Excitadores, Insurgentes Sur 3877, Col. La Fama, México, D.F. C.P. 14-269, Mexico.
authors.forename: Mario Israel
authors.initials: MI
authors.lastname: Pérez-Padrón
authors.affiliation: Instituto Nacional de Neurología y Neurocirugía, Laboratorio de Neuroinmunología, Insurgentes Sur 3877, Col. La Fama, México, D.F. C.P. 14-269, Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Guevara-Salazar
authors.affiliation: Instituto Nacional de Neurología y Neurocirugía, Laboratorio de Aminoácidos Excitadores, Insurgentes Sur 3877, Col. La Fama, México, D.F. C.P. 14-269, Mexico.
authors.forename: Irma Gabriela
authors.initials: IG
authors.lastname: González-Herrera
authors.affiliation: Instituto de Investigaciones en Materiales, Laboratorio de Materiales Funcionales Orgánicos, Universidad Nacional Autónoma de México, C.P. 70-360, CU, Coyoacán, México D.F. 04510, Mexico. Electronic address: patriciagua@iim.unam.mx.
authors.forename: Patricia
authors.initials: P
authors.lastname: Guadarrama
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051381:Rats; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000975:Antioxidants; D003603:Cytotoxins; D014867:Water; D003474:Curcumin
keywords: Antioxidant capacity; Curcumin; Polyester dendrons; Solubility enhancement