CURCUMIN, THE GOLDEN POWDER FROM TURMERIC: INSIGHTS INTO CHEMICAL AND BIOLOGICAL ACTIVITIES

Turmeric, obtained from the dried rhizomes of Curcuma longa (Zingiberaceae), is a golden colored material, commonly used around the world for seasoning and coloring food dishes. Since antiquity, turmeric has been widely used in the treatment of several diseases in traditional Chinese and Indian medicine (Ayurveda), where it is also known by other names such as Kanchani (goddess gold) or also Gauri (having a bright and luminous face), a designation stemming from the gilded appearance of the plant material. Curcumin, the main chemical component of turmeric, is responsible both for its properties as dyes as well as its biological activities. This diarylheptanoid was first isolated almost two centuries ago and had its chemical structure determined in 1910 as being diferuloylmethane. Subsequently, more detailed and relevant data were obtained furthering the understanding of structural features of curcumin. The classical methodology for the synthesis of curcumin and other curcuminoids was described in 1960 by Pabon. Subsequently, different variations on this methodology have been developed, culminating with the synthesis of different curcuminoids. Several studies have been published in recent years on the biological activities exhibited by curcumin including its antioxidant, antitumor, anti-inflammatory, antiviral, antibacterial, antifungal, antimalarial and leishmanicidal activities

2-Chloro-4,6-bis{(E)-3-methoxy-4-[(4-methoxybenzyl)oxy]styryl}pyrimidine: Synthesis, Spectroscopic and Computational Evaluation

A novel curcumin analog namely 2-chloro-4,6-bis{(E)-3-methoxy-4-[(4-methoxybenzyl)oxy]- styryl}pyrimidine (compound 7) was synthesized by three-step reaction. The condensation reaction of protected vanillin with 2-chloro-4,6-dimethylpyrimidine (6) was the most efficient step, resulting in a total yield of 72%. The characterization of compound 7was performed by 1Hand 13C nuclearmagnetic resonance (NMR), as well as high-resolution mass spectrometry. The experimental spectrometric data were compared with the theoretical spectra obtained by the density functional theory (DFT) method, showing a perfectmatch between them.UV-visible spectroscopy and steady-state fluorescence emission studies were performed for compound 7 in solvents of different polarities and the results were correlated with DFT calculations. Compound 7 showed a solvatochromism effect presenting higher molar extinction coefficient (log " = 4.57) and fluorescence quantum yield ( = 0.38) in toluene than in acetonitrile or methanol. The simulation of both frontier molecular orbitals (FMOs) and molecular electrostatic potential (MEP) suggested that the experimental spectra profile in toluene was not interfered by a possible charge transfer. These results are an indication of a low probability of compound 7 in reacting with unsaturated phospholipids in future applications as a fluorescent dye in biological systems

The Effectiveness of Natural Diarylheptanoids against <i>Trypanosoma cruzi</i>: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies

<div><p>Curcumin (CUR) is the major constituent of the rhizomes of <i>Curcuma longa</i> and has been widely investigated for its chemotherapeutic properties. The well-known activity of CUR against <i>Leishmania sp</i>., <i>Trypanosoma brucei</i> and <i>Plasmodium falciparum</i> led us to investigate its activity against <i>Trypanosoma cruzi</i>. In this work, we tested the cytotoxic effects of CUR and other natural curcuminoids on different forms of <i>T</i>. <i>cruzi</i>, as well as the ultrastructural changes induced in epimastigote form of the parasite. CUR was verified as the curcuminoid with more significant trypanocidal properties (IC₅₀ 10.13 μM on epimastigotes). Demethoxycurcumin (DMC) was equipotent to CUR (IC₅₀ 11.07 μM), but bisdemethoxycurcumin (BDMC) was less active (IC₅₀ 45.33 μM) and cyclocurcumin (CC) was inactive. In the experiment with infected murine peritoneal macrophages all diarylheptanoids were more active than the control in the inhibition of the trypomastigotes release<b>.</b> The electron microscopy images showed ultrastructural changes associated with the cytoskeleton of the parasite, indicating tubulin as possible target of CUR in <i>T</i>. <i>cruzi</i>. The results obtained by flow cytometry analysis of DNA content of the parasites treated with natural curcuminoids suggested a mechanism of action on microtubules related to the paclitaxel`s mode of action. To better understand the mechanism of action highlighted by electron microscopy and flow cytometry experiments we performed the molecular docking of natural curcuminoids on tubulin of <i>T</i>. <i>cruzi</i> in a homology model and the results obtained showed that the observed interactions are in accordance with the IC₅₀ values found, since there CUR and DMC perform similar interactions at the binding site on tubulin while BDMC do not realize a hydrogen bond with Lys163 residue due to the absence of methoxyl groups. These results indicate that trypanocidal properties of CUR may be related to the cytoskeletal alterations.</p></div

Structures of the main chemical constituents from <i>Curcuma longa</i>.

<p>Structures of the main chemical constituents from <i>Curcuma longa</i>.</p

Murine peritoneal macrophages were infected with 10⁵ <i>T</i>. <i>cruzi</i> trypomastigotes (Dm28c strain).

<p>Parasite cultures were treated with 100 μM of benznidazole, CUR, DMC, BDMC and CC. After 7 days, the number of released trypomastigotes in the culture medium were determined. The data shown were obtained from three independent experiments. Cultures were compared using unpaired T-Student test (Graph Pad Prism). *P<0.05.</p

Superposition of best qualified poses of CUR (Entry A), DMC (Entry B) and BDMC (Entry C) after docking into <i>T</i>. <i>cruzi</i> tubulin.

<p>Hydrogen atoms were omitted for clarity; carbon atoms in green: tubulin; yellow: CUR; cyan: DMC; magenta: BDMC. (image generated with PyMOL, DeLano Scientific LLC)</p

ChemPLP scores and hydrogen bond distances for curcumin derivatives from docking into <i>T</i>. <i>cruzi</i> tubulin.

<p>ChemPLP scores and hydrogen bond distances for curcumin derivatives from docking into <i>T</i>. <i>cruzi</i> tubulin.</p

Scanning electron microscopy of <i>T</i>. <i>cruzi</i> epimastigotes.

<p>Untreated control cells (A) displayed the usual elongated morphology with smooth cell surface. Parasites incubated with 10.13 μM curcumin for 24 h (B-D) presented reduced cell volume (B) as well as cell body rounding with multiple longitudinal invaginations involving the anterior portion of the parasite (C,D). Some cells displayed multiple shortened flagella (C, arrows). The protrusion of flagellar membrane was detected (D, arrows).</p