Curcumin Ligand Research Articles

The in vitro antitumor activity of arene-ruthenium(II) curcuminoid complexes improves when decreasing curcumin polarity

The antitumor activity of ruthenium(II) arene (p-cymene, benzene, hexamethylbenzene) derivatives containing modified curcumin ligands (HCurcI=(1E,4Z,6E)-5-hydroxy-1,7-bis(3,4-dimethoxyphenyl)hepta-1,4,6-trien-3-one and HCurcII=(1E,4Z,6E)-5-hydroxy-1,7-bis(4-methoxyphenyl)hepta-1,4,6-trien-3-one) is described. These have been characterized by IR, ESI-MS and NMR spectroscopy. The X-ray crystal structure of HCurcI has been determined and compared with its related Ru complex. Four complexes have been evaluated against five tumor cell lines, whose best activities [IC50 (μM)] are: breast MCF7, 9.7; ovarian A2780, 9.4; glioblastoma U-87, 9.4; lung carcinoma A549, 13.7 and colon-rectal HCT116, 15.5; they are associated with apoptotic features. These activities are improved when compared to the already known corresponding curcumin complex, (p-cymene)Ru(curcuminato)Cl, about twice for the breast and ovarian cancer, 4.7 times stronger in the lung cancer and about 6.6 times stronger in the glioblastoma cell lines. In fact, the less active (p-cymene)Ru(curcuminato)Cl complex only shows similar activity to two novel complexes in the colon cancer cell line. Comparing antitumor activity between these novel complexes and their related curcuminoids, improvement of antiproliferative activity is seen for a complex containing CurcII in A2780, A549 and U87 cell lines, whose IC50 are halved. Therefore, after replacing OH curcumin groups with OCH3, the obtained species HCurcI and its Ru complexes have increased antitumor activity compared to curcumin and its related complex. In contrast, HCurcII is less cytotoxic than curcumin but its related complex [(p-cymene)Ru(CurcII)Cl] is twice as active as HCurcII in 3 cell lines. Results from these novel arene-Ru curcuminoid species suggest that their increased cytotoxicity on tumor cells correlate with increase of curcuminoid lipophilicity.

Substituted phenylhydrazono derivatives of curcumin as new ligands, a theoretical study

A family of phenylhydrazono curcumin ligands was studied to see the influence of the substituents over the composition of the molecular orbitals, electronic transitions and reactivity by means of DFT and TDDFT calculations. The substituents varied between electron-donor groups (EDG) to electron-withdrawing groups (EWG). The geometrical parameters remain almost unchanged when the character of the substituent was changed. On the other hand the HOMO, LUMO and HOMO–LUMO gap (HLG) energies changed dramatically. TDDFT calculations were performed in order to propose the main absorption bands of this family of compounds. All the obtained showed a good correlation with a Hammett correlation.

Synthesis and Characterization of some Ternary Metal Complexes of Curcumin with 1,10-phenanthroline and their Anticancer Applications

Some ternary complexes of curcumin have been synthesized by the reaction of M(II) nitrate with curcumin as primary ligand and 1,10-phenanthroline (phen) as supporting ligand in water/ethanol solution under a nitrogen atmosphere. The composition of the complexes has been characterized by elemental analysis, molar conductivity, thermogravimetric analysis, IR, UV–vis spectroscopy. The results reveal that curcumin ligand coordinates with M(II) in bidentate mode after deprotonation. The supporting ligand (phen) uses its two N atoms in coordination with metal ions in bidentate mode. The general formula of the complexes is [M(Cur)(phen)]NO3 (M = Ni(II), Co(II), Cu(II) and Z(II)). The results of antibacterial activity indicated that the complexes have good antibacterial ability for the testing bacterium than that of curcumin. Furthermore, the [M(Cur)(phen)]NO3 complexes were evaluated for its in vitro anticancer activity against hepatocellular carcinoma. © 2014 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved. doi: http://dx.doi.org/10.3329/jsr.v6i3.18750 J. Sci. Res. 6 (3), 509-519 (2014)

Synthesis, Characterization, Mössbauer Parameters, and Antitumor Activity of Fe(III) Curcumin Complex

Curcumin-Fe(III) complex was prepared from Fe(NO3)3 ·9H2O precursor and curcumin by refluxing a slightly basic methanolic solution of their mixture with the objective of investigating its cytotoxicity. The enol form of curcumin ligand was established by FTIR, UV/Vis, 1H NMR, and 13C NMR spectroscopy. The as-prepared product was characterized by elemental analysis, FTIR, UV, and Mössbauer spectroscopic techniques. An octahedral high-spin Fe(III) complex was obtained, δ, 0.37 mms−1; Q.S., 0.79 mms−1; no magnetic relaxation was observed at liquid N2 temperature, neither reduction of Fe(III). The tested cytotoxicity of the as-prepared complex on four cancer cell lines indicated inhibition of the curcumin activity upon complexing with iron.

Synthesis and characterization of ligational behavior of curcumin drug towards some transition metal ions: Chelation effect on their thermal stability and biological activity

Complexes of Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) with curcumin ligand as antitumor activity were synthesized and characterized by elemental analysis, conductometry, magnetic susceptibility, UV–Vis, IR, Raman, ESR, 1H-NMR spectroscopy, X-ray diffraction analysis of powdered samples and thermal analysis, and screened for antimicrobial activity. The IR spectral data suggested that the ligand behaves as a monobasic bidentate ligand towards the central metal ion with an oxygen’s donor atoms sequence of both OH and CO groups under keto–enol structure. From the microanalytical data, the stoichiometry of the complexes 1:2 (metal:ligand) was found. The ligand and their metal complexes were screened for antibacterial activity against Escherichia Coli, Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa and fungicidal activity against Aspergillus flavus and Candida albicans.

Density functional theory investigation of Cu(I)‐ and Cu(II)‐curcumin complexes

Density functional theory is used to obtain the lowest energy geometries of bis-aqua curcumin complexes and bis-curcumin complexes of Cu(I) and Cu(II). Three conformations of curcumin, obtained by rotation of the substituted aromatic groups, were considered in each case. Steric repulsion, due to the methoxy–methoxy interactions, was found to be an important factor in determining the lowest energy conformer of Cu(II)(curcumin)2 but was less important for the Cu(I) analog. Using a sufficiently large basis set, the results show that the lowest energy Cu(II)(curcumin)2 geometry is square planar around the copper atom, in contrast to the results from a previous study (Shen et al. THEOCHEM-J Mol Struct 2005, 757, 199). In addition, other studies suggested that the formation of this complex is followed by the reduction of Cu(II) to Cu(I). We also examined the singly occupied molecular orbital, spin density, and natural bond orbitals of Cu(II)(curcumin)2. While the former two analyses show little evidence of electron transfer from curcumin into the Cu center, the latter indicates that Cu(II) is partially reduced to Cu(I) as a consequence of complexation. Finally, we consider the bis-aqua curcumin and bis-curcumin complexes on a reaction path involving progressive displacement of water molecules by curcumin ligands. The results show that the bis-curcumin complex is the most stable Cu(II) complex, showing consistently exothermic steps in the reaction path. However, for Cu(I), the final step in the reaction path is essentially thermoneutral, indicating that the 1:1 and 1:2 Cu(I) complexes are equally stable thermodynamically.