33171-05-0Relevant articles and documents
Preparation method 1,7 - di (4 -hydroxy) heptyl -3-5 - glycol ester
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, (2021/01/30)
The invention discloses a preparing method of 1,7-bis(4-benzene hydroxyl)heptyl-3,5-glycol ester. The method includes the following steps of firstly, conducting a -C=C- reduction reaction with bisdemethoxycurcumin as the raw material to obtain a product 3; secondly, conducting a reduction reaction of carbonyl on the premise of protecting hydroxyl on a benzene ring to obtain a product 5; secondly,conducting an esterification reaction on the product 5 to obtain a product 6, and conducting a protecting group removing reaction on the product 6 to obtain the final product, namely 1,7-bis(4-benzenehydroxyl)heptyl-3,5-glycol ester. By means of the method, through the reduction reaction, the reaction of protecting hydroxyl on the benzene ring, the reaction of reducing carbonyl, the esterification reaction and the protecting group removing reaction, 1,7-bis(4-benzene hydroxyl)heptyl-3,5-glycol ester can be obtained; the reaction process is simple, operation is simple, applied raw materials are low in cost, yield is high, and the method is suitable for industrially producing 1,7-bis(4-benzene hydroxyl)heptyl-3,5-glycol ester on a large scale.
Curcumin derivatives as photosensitizers in photodynamic therapy: Photophysical properties and: In vitro studies with prostate cancer cells
Kazantzis,Koutsonikoli,Mavroidi,Zachariadis,Alexiou,Pelecanou,Politopoulos,Alexandratou,Sagnou
, p. 193 - 206 (2020/03/03)
Photodynamic therapy (PDT) is a minimally invasive approach to treat various forms of cancer, based on the ability of certain non-toxic molecules (photosensitizers) to generate reactive oxygen species (ROS) after excitation by light of a certain wavelength and eventually induce strong phototoxic reactions against malignant cells and other pathogens. Curcumin is one of the most extensively investigated phytochemicals with a wide range of therapeutic properties and has been shown to induce strong photocytotoxic effects in micromolar concentrations against a variety of cancer cell lines. Curcumin (1) is comparatively evaluated with the naturally occurring bisdemethoxy Curcumin (2), which lacks the two methoxy groups, as well as two newly synthesized curcuminoids, the cinnamaldehyde derivative (3) and the dimethylamino one (4), designed to increase the absorption maximum and hence the tissue penetration. The synthetic curcuminoids were successfully synthesized in sufficient amounts and their photophysical properties such as absorption, fluorescence, photobleaching and free radical generation were investigated. Compound 4 exhibited a significant increase in peak absorption (497 nm) and strong fluorescent emission signals were recorded for all curcuminoids. Photobleaching of 4 was comparable to 1 whereas 2 and 3 showed more extended photobleaching but much higher ROS production in very short irradiation times. Compounds 2 and 4 exhibited specific intracellular localization. After dark and light cytotoxicity experiments against LNCaP prostate cancer cell line for all curcuminoids, concentration of 3 μM and irradiance of 6 mW cm-2 were selected for the PDT application which resulted in remarkable results with very short LD50. Curcuminoids 2 and 4 exhibited a significant dose-dependent PDT effect. The biphasic dose-response photodynamic effect observed for 1 and 3 may provide a strategy against prolonged and sustained photosensitivity.
Method for artificially synthesizing curcumin and derivatives thereof
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Paragraph 0026-0027; 0031-0032; 0050-0052, (2020/05/30)
The invention provides a method for artificially synthesizing curcumin and derivatives thereof. The method comprises the following steps: reacting acetylacetone with boron oxide under a weakly acidiccondition to generate a complex, protecting methylene groups between two ketocarbonyl groups, adding a catalyst, reacting the complex with vanillin (benzaldehyde derivative) to obtain a curcumin derivative intermediate (I), and hydrolyzing the intermediate to obtain the curcumin derivative. The selectivity of the reaction is far higher than that of a preparation reaction in an alkaline system, andis macroscopically and specifically embodied in the yield of curcumin and derivatives thereof: in the existing two-pot reaction, the yield of curcumin in the whole process is about 60%; the yield ofthe preparation method can reach 80-90%. Therefore, the method provided by the invention reduces the waste of raw materials and the generation of byproducts; and complete hydrolysis can be realized only at normal temperature, insoluble substances included in the product are almost zero, and the obtained product is pure.
Synthesis, characterization and ROS-mediated antitumor effects of palladium(II) complexes of curcuminoids
Li, Yanci,Gu, Zhenyu,Zhang, Can,Li, Shenghui,Zhang, Liang,Zhou, Guoqiang,Wang, Shuxiang,Zhang, Jinchao
, p. 662 - 671 (2018/01/01)
Based on the synthesis of curcumin and its derivatives from aromatic aldehydes, a novel series of palladium(II) complexes with curcumin (or its derivatives) and 2,2′-bipyridine have been synthesized through a directed self-assembly approach that involves spontaneous deprotonation of the curcuminoid ligands in H2O/acetone solution. These complexes have been characterized by 1H (13C) NMR, HRMS and elemental analysis. Crystal structure of 3h has been determined by X-ray diffraction analysis. Their cytotoxicity was tested by MTT. The preliminary results showed that complexes 3d, 3f, 3h have significant inhibition on proliferation of three carcinoma cells such as MCF-7, HeLa and A549 cells, which were more active than cisplatin. Further mechanistic studies indicated that the tested complex 3h arrested the cell cycle in the S phase and can disrupted mitochondrial membrane potential and induced tumor cell apoptosis through reactive oxygen species (ROS)-dependent pathway.
Structure-Activity Relationship of Curcumin: Role of the Methoxy Group in Anti-inflammatory and Anticolitis Effects of Curcumin
Yang, Haixia,Du, Zheyuan,Wang, Weicang,Song, Mingyue,Sanidad, Katherine,Sukamtoh, Elvira,Zheng, Jennifer,Tian, Li,Xiao, Hang,Liu, Zhenhua,Zhang, Guodong
, p. 4509 - 4515 (2017/06/13)
Curcumin, a dietary compound from turmeric, has beneficial effects on inflammatory diseases such as inflammatory bowel disease. Most previous studies have focused on the structure-activity relationship of the thiol-reactive α,β-unsaturated carbonyl groups of curcumin, so little is known about the roles of methoxy groups in biological activities of curcumin. Here we synthesized a series of curcumin analogues with different substitution groups (R = H-, Br-, Cl-, F-, NO2-, CH3-, and OH-) to replace the methoxy group and evaluated their biological effects in vitro and in vivo. Curcumin, Cur-OH, and Cur-Br (25 μM) suppressed 74.91 ± 0.88, 77.75 ± 0.89, and 71.75 ± 0.90% of LPS-induced NO production, respectively (P 2, were inactive (P > 0.05). In the dextran sulfate sodium (DSS)-induced colitis mouse model, the Cur-Br analogue also showed a beneficial effect the same as curcumin (P 2 analogue had no effect in the animal model (P > 0.05). Together, the analogues have dramatically different effects on inflammation, supporting that the substitution group on the methoxy position plays an important role in the anti-inflammatory effects of curcumin. The methoxy group is a potential structural candidate for modification to design curcumin-based drugs for inflammatory diseases.
Synthesis, spectral characterization and thermal analysis of rubrocurcumin and its analogues
John, Jeena,Devi, R. Sudha,Balachandran,Babu, K. V. Dinesh
, p. 2301 - 2314 (2017/10/06)
Rubrocurcumin and its analogues were synthesized and characterized by UV, IR, NMR and FT-MS spectral data. Thermal analysis of compounds has been carried out using TG-DTG techniques using non-isothermal heating conditions. Flynn–Wall–Ozawa and Kissinger–Akahira–Sunose isoconversional methods were used to determine the apparent activation energies (Ea) for the thermal decomposition rubrocurcumin and its analogues. The Ea values obtained using these methods were used as reference to determine the most suitable kinetic model using Coats–Redfern method. A possible mechanism is suggested to explain the thermal decomposition process. From the TG-DTG data, kinetic parameters have been calculated and were used to evaluate the thermal stability of compounds and the substituent effect on its thermal stability.
3,3′-OH curcumin causes apoptosis in HepG2 cells through ROS-mediated pathway
Liu, Guo-Yun,Sun, Yong-Zheng,Zhou, Na,Du, Xiu-Mei,Yang, Jie,Guo, Shang-Jing
, p. 157 - 163 (2018/05/25)
In this paper, we synthesized a series of curcumin analogs and evaluated their cytotoxicity against HepG2 cells. The results exhibited that the hydroxyl group at 3,3′-position play an essential role in enhancing their anti-proliferation activity. More importantly, 3,3′-hydroxy curcumin (1b) caused apoptosis in HepG2 cells with the ROS generation, which may be mainly composed of hydroxyl radicals (HO[rad]) and H2O2. The more cytotoxic activity and ROS-generating ability of 1b may be due to the more stable in (RPMI)-1640 medium and more massive uptake than curcumin. Then the generation of ROS can disrupt the intracellular redox balance, induce lipid peroxidation, cause the collapse of the mitochondrial membrane potential and ultimately lead to apoptosis. The results not only suggest that 3,3′-hydroxy curcumin (1b) may cause HepG2 cells apoptosis through ROS-mediated pathway, but also offer an important information for design of curcumin analog.
The effectiveness of natural diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, ultrastructural alterations and molecular modeling studies
Sueth-Santiago, Vitor,De Moraes, Jullianede B. B.,Alves, Eliomara Sousa Sobral,Vannier-Santos, Marcos Andre,Freire-De-lima, Celio G.,Castro, Rosane N.,Mendes-Silva, Gustavo Peron,De Nigris Del Cistia, Catarina,Magalh?es, Luma Godoy,Andricopulo, Adriano Defini,Santánna, Carlos Mauricio R.,Decote-Ricardo, Debora,Edilsonfreiredelima, Marco
, (2016/10/26)
Curcumin (CUR) is the major constituent of the rhizomes of Curcuma longa and has been widely investigated for its chemotherapeutic properties. The well-known activity of CUR against Leishmania sp., Trypanosoma brucei and Plasmodium falciparum led us to investigate its activity against Trypanosoma cruzi. In this work, we tested the cytotoxic effects of CUR and other natural curcuminoids on different forms of T. cruzi, 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. The electron microscopy images showed ultrastructural changes associated with the cytoskeleton of the parasite, indicating tubulin as possible target of CUR in T. cruzi. 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 T. cruzi 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.
Synthesis and cytotoxic activities of a curcumin analogue and its bis-Mannich derivatives
Yerdelen, Kadir Ozden,Gul, Halise Inci,Sakagami, Hiroshi,Umemura, Naoki,Sukuroglu, Murat
, p. 643 - 649 (2015/09/01)
Mannich bases (2-6) of curcumin analogue 1, [1,5-bis(4-hydroxy-phenyl)penta-1,4-dien-3-one], were synthesized.Their cytotoxicity against human HL-60 promyelocytic leukemia and HSC-2, HSC-3, and HSC-4 oral squamous carcinoma cell lines, as well as against normal oral cells was evaluated. Mannich bases 2-5 displayed more potent cytotoxicity than curcumin and curcumin analogue 1 towards malignant cells with high PSE values (93.7-136.6). PARP1 cleavage assay demonstrated the induction of apoptosis of HSC-2 cells by the most potent and tumor selective compound 4, which is a bis Mannich base having N-methyl piperazine moieties. The results obtained suggest that preparation of Mannich bases of a curcumin analogue 1 was a useful chemical modification for cytotoxicity and tumour-selectivity for the compounds synthesized, and apoptosis can be one of the possible mechanisms of action for the cytotoxicity.
Photoactivated cytotoxicity of ferrocenyl-terpyridine oxovanadium(IV) complexes of curcuminoids
Balaji, Babu,Balakrishnan, Babita,Perumalla, Sravanakumar,Karande, Anjali A.,Chakravarty, Akhil R.
, p. 458 - 467 (2014/11/08)
Oxovanadium(IV) complexes, viz. [VO(Fc-tpy)(Curc)](ClO4) (1), [VO(Fc-tpy)(bDHC)](ClO4) (2), [VO(Fc-tpy)(bDMC)](ClO4) (3) and [VO(Ph-tpy)(Curc)](ClO4) (4), of 4′-ferrocenyl-2,2′: 6′,2″-terpyridine (Fc-tpy) and 4′-phenyl-2,2′:6′, 2″-terpyridine (Ph-tpy) and monoanionic curcumin (Curc), bis-dehydroxycurcmin (bDHC) and bis-demethoxycurcumin (bDMC) were prepared, characterized and their photo-induced DNA cleavage activity and photocytotoxicity in visible light studied. The ferrocenyl complexes 1-3 showed an intense metal-to-ligand charge transfer band near 585 nm in DMF and displayed Fc+/Fc and V(IV)/V(III) redox couples near 0.65 V and -1.05 V vs. SCE in DMF-0.1 M TBAP. The complexes as avid binders to calf thymus DNA showed significant photocleavage of plasmid DNA in red light of 647 nm forming OH radicals. The complexes showed photocytotoxicity in HeLa and Hep G2 cancer cells in visible light of 400-700 nm with low dark toxicity. ICP-MS and fluorescence microscopic studies exhibited significant cellular uptake of the complexes within 4 h of treatment with complexes. The treatment with complex 1 resulted in the formation of reactive oxygen species inside the HeLa cells which was evidenced from the DCFDA assay.
