579-23-7Relevant academic research and scientific papers
A synthetic curcuminoid derivative inhibits nitric oxide and proinflammatory cytokine synthesis
Tham, Chau Ling,Liew, Choi Yi,Lam, Kok Wai,Mohamad, Azam-Shah,Kim, Min Kyu,Cheah, Yoke Kqueen,Zakaria, Zainul-Amirudin,Sulaiman, Mohd-Roslan,Lajis, Nordin H.,Israf, Daud A.
, p. 247 - 254 (2010)
Curcumin is a highly pleiotropic molecule with significant regulatory effects upon inflammation and inflammatory related diseases. However curcumin has one major important limitation in which it has poor bioavailability. Design of synthetic structural derivatives of curcumin is but one approach that has been used to overcome its poor bioavailability while retaining, or further enhancing, its drug-like effects. We have synthesized a series of curcumin analogues and describe the effects of 2,6-bis-4-(hydroxyl-3-methoxy-benzylidine)-cyclohexanone or BHMC upon nitric oxide and cytokine synthesis in cellular models of inflammation. BHMC showed a significant dose-response inhibitory action upon the synthesis of NO and we have shown that this effect was due to suppression of both iNOS gene and enzyme expression without any effects upon scavenging of nitrite. We also demonstrated that BHMC has a very minimal effect upon iNOS activity with no effect at all upon the secretion of PGE2 but has a strong inhibitory effect upon MCP-1 and IL-10 secretion and gene expression. Secretion and gene expression of TNF-α and IL-6 were moderately inhibited whereas IL-8 and IL-1β were not altered. We conclude that BHMC selectively inhibits the synthesis of several inflammatory mediators. BHMC should be considered a promising drug lead for preclinical and further pharmacological studies.
Cinnamoyl compounds as simple molecules that inhibit p300 histone acetyltransferase
Costi, Roberta,Di Santo, Roberto,Artico, Marino,Miele, Gaetano,Valentini, Paola,Novellino, Ettore,Cereseto, Anna
, p. 1973 - 1977 (2007)
Cinnamoly compounds 1a-c and 2a-d were designed, synthesized, and in vitro tested as p300 inhibitors. At different degrees, all tested compounds were proven to inactivate p300, particularly, derivative 2c was the most active inhibitor, also showing high specificity for p300 as compared to other histone acetyltransferases. Most notably, 2c showed anti-acetylase activity in mammalian cells. These compounds represent a new class of synthetic inhibitors of p300, characterized by simple chemical structures.
Inhibition of dengue virus by curcuminoids
Balasubramanian, Anuradha,Pilankatta, Rajendra,Teramoto, Tadahisa,Sajith, Ayyiliath M.,Nwulia, Evaristus,Kulkarni, Amol,Padmanabhan, Radhakrishnan
, p. 71 - 78 (2019)
The dengue virus is considered to be a globally important human pathogen prevalent in tropical and subtropical regions of the world. According to a recent estimate, the disease burden due to DENV infections is ～390 million infections per year globally in ～100 countries including the southern US, Puerto Rico and Hawaii, resulting in nearly ～25,000 deaths mostly among children. Despite the significant morbidity and mortality that results from DENV infections, there is currently no effective chemotherapeutic treatment for DENV infections. We identified curcumin as an inhibitor of DENV2 NS2B/NS3protease in a previous high-throughput screening (HTS) campaign. We synthesized four analogues of curcumin (curcuminoids) and tested the in vitro protease inhibition activity and inhibition of replication by cell-based assays. The results revealed that curcumin is a weak inhibitor of the viral protease. However, the analogues exhibited more potent inhibition of DENV infectivity in plaque assays suggesting that the cellular pathway(s) required for viral replication and/or assembly are targeted by these compounds. Further analysis shows that inhibition of genes involved in lipid biosynthesis, and of actin polymerization by curcuminoids, are likely to be involved as their mode of action in DENV2-infected cells. Three of the curcumin derivatives possess good selectivity indices (SI) (>10) when compared to the parent curcumin.
Curcumin and a hemi-analogue with improved blood–brain barrier permeability protect against amyloid-beta toxicity in Caenorhabditis elegans via SKN-1/Nrf activation
Lee, Elaine Hui-Chien,Lim, Sherlyn Sheau-Chin,Yuen, Kah-Hay,Lee, Chong-Yew
, p. 860 - 868 (2019)
Objectives: This study aims to investigate the blood–brain barrier (BBB) permeability of curcumin analogues with shortened linkers and their ability to protect against amyloid-beta toxicity in a whole organism model. Method: Four curcumin analogues were synthesized. These analogues and curcumin were evaluated for their BBB permeability in the parallel artificial membrane permeability assay. The transgenic Caenorhabditis elegansGMC101 that expresses human Aβ1–42 was treated with the compounds to evaluate their ability to delay Aβ-induced paralysis. Expression of skn-1mRNA was examined on nematodes treated with selected efficacious compounds. In vitro Aβ aggregation in the presence of the compounds was performed. Key findings: The four analogues showed improved BBB permeability vs curcumin in the PAMPA with the hemi-analogue C4 having the highest permeability coefficient. At 100 μm, analogues C1 and C4 as well as curcumin significantly prolonged the survival of the nematodes protecting against Aβ toxicity. However, only curcumin and C4 showed protection at lower concentrations. skn-1mRNA was significantly elevated in nematodes treated with curcumin and C4 indicating SKN-1/Nrf activation as a possible mode of action. Conclusions: Analogue C4 provides a new lead for the development of a curcumin-based compound for protection against Aβ toxicity with an improved BBB permeability.
The: In vivo anti-tumor effect of curcumin derivative (2 E,6 E)-2,6-bis(4-hydroxy-3-methoxybenzylidene)cyclohexanone (BHMC) on 4T1 breast cancer cells
Razak, Nursyamirah Abd,Akhtar, M. Nadeem,Abu, Nadiah,Ho, Wan Yong,Tan, Sheau Wei,Zareen, Seema,Taj-Ud-Din, Saiful Nizam Bin,Long, Kamariah,Alitheen, Noorjahan Banu,Yeap, Swee Keong
, p. 36185 - 36192 (2017)
Curcumin is one of the promising natural products extracted from the rhizomes of curcuma longa and has been extensively investigated by researchers to explore its potential as a chemopreventive and therapeutic agent against several chronic diseases. To further enhance the cytotoxic potential of curcumin, its derivative (2E,6E)-2,6-bis(4-hydroxy-3-methoxybenzylidene)cyclohexanone (BHMC) has been synthesized and investigated, and its antitumor effect on tested on 4T1 challenged mice. BHMC was recorded with in vitro cytotoxicity on murine 4T1 breast cancer cells with IC50 value 13.66 μM, which was 2 times lower than curcumin after 72 hours of treatment. An in vivo study indicated that BHMC possessed antitumor effect on the 4T1 cells of the challenged mice by induction of apoptosis, antiproliferation, anti-inflammation and antimetastasis. This effect is better compared to curcumin treatment at the same evaluated concentration. Thus, BHMC is a potential antitumor agent against breast cancer.
Novel polyesters based on indazole moiety: Synthesis, characterization and applicability as efficient inhibitors for acidic X-65-steel corrosion
Abd El-Lateef, Hany M.,Aly, Kamal I.,El-Remaily, Mahmoud Abd El Aleem Ali Ali,Khodairy, A.,Sayed, Marwa M.,Yehia, Nasr
, (2021/08/07)
In this report, novel series of unsaturated polyesters Va-d and VIa-d containing indazole moiety were successfully prepared via interfacial polycondensation technique of indazole derivatives III and IV with different aromatic and aliphatic acid chlorides; isophthaloyl-, terephthaloyl-, adipoyl-, and sebacoyl chlorides. The prepared polyesters were categorized by elemental analyses, IR, 1H NMR, Mass spectra, GPC, Thermogravimetric (TGA), X-ray analyses (XRD), and therefore the morphology was examined by scanning microscopy (SEM). They showed high thermal stability and different morphology structure. The corrosion protection performance of prepared polyesters Va-d and VIa-d on X65-steel in molar oil of vitriol was assessed using potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS), and SEM. Electrochemical tests (EIS and PDP) displayed polymers could efficiently impede the X65-steel corrosion and acted as inhibitors of the mixed type. At the optimal dose of 150 mg/L, the protection capacities of Va-d and VIa-d polymers ranged from 86.9% to 97.8%. adsorption of Va-d and VIa-d followed the adsorption model of Langmuir isotherm. Surface morphology examination by SEM also revealed that Va-d and VIa-d polymers form an efficient block layer on the surface of X65-steel to separate the acidic solution.
Synthesis, characterization, and antioxidant activity of some 2-methoxyphenols derivatives
Al Ajeil, Ruba,AlNeyadi, Shaikha S.,Amer, Naheed,Breitener, Priya,Munawar, N.,Thomas, Tony G.
, p. 112 - 122 (2020/10/23)
Oxidative stress is a causative factor in the pathophysiology of numerous diseases, such as diabetes, atherosclerosis, cancer, and neurodegenerative and cardiovascular diseases. Therapeutic antioxidants are promising candidates for preventing and treating conditions in which oxidative stress is a contributing factor. In this study, we report the design, synthesis and antioxidant activity of six compounds containing the 2-methoxyphenol moiety core structure. The synthesized derivatives were characterized using 1H NMR, 13C NMR, Fourier-transform infrared (FT-IR), and elemental analysis spectroscopy. The antioxidant properties of the compounds were evaluated using the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and oxygen radical absorbance capacity (ORAC) assay. New phenolic acid-derived compounds with antioxidant activity were identified.
Cytotoxicity of some synthetic bis(arylidene) derivatives of cyclic ketones towards cisplatin-resistant human ovarian carcinoma cells
Fasanya, Olatunde,Javid, Farideh,Mothia, Begum,Patel, Hinal,Patel, Jaison,Sooda, Kartheek,Wyatt, Peter B.
, (2020/05/05)
Symmetrical α,α?-bis(arylidene)ketones were prepared by acid-catalyzed aldol condensations between aliphatic ketones (e.g., cyclopentanone, 4-alkylcyclohexanones, tetrahydropyran-4-one, and tetrahydrothiopyran-4-one) and two equivalents of an aromatic hydroxyaldehyde (e.g., 4-hydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, vanillin, isovanillin, and 3-fluoro-4-hydroxybenzaldehyde). Most of the compounds were cytotoxic towards the cisplatin-resistant human ovarian cancer cell line A2780-CP70 as well as the non-resistant line A2780.
Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin
Deck, Lorraine M.,Hunsaker, Lucy A.,Vander Jagt, Thomas A.,Whalen, Lisa J.,Royer, Robert E.,Vander Jagt, David L.
, p. 854 - 865 (2017/12/13)
Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a number of clinical studies with limited success, mainly owing to limited bioavailability and rapid metabolism. Enone analogues of curcumin were examined with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of Nrf2 were found in all three groups, many of which were more active than curcumin. Dose-response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues.
Synthesis, biological evaluation, QSAR and molecular dynamics simulation studies of potential fibroblast growth factor receptor 1 inhibitors for the treatment of gastric cancer
Ying, Shilong,Du, Xiaojing,Fu, Weitao,Yun, Di,Chen, Liping,Cai, Yuepiao,Xu, Qing,Wu, Jianzhang,Li, Wulan,Liang, Guang
, p. 885 - 899 (2017/02/18)
Accumulating evidence suggests that fibroblast growth factor receptor 1 (FGFR1) is an attractive target in gastric cancer therapy. Based on our previous discovery of two non-ATP competitive FGFR1 inhibitors, A114 and A117, we designed and screened a series of compounds with the framework of bisaryl-1,4-dien-3-one. Among them, D12 and D15 exhibited the most potent FGFR1 inhibitory activity, which was ATP-independent. Furthermore, a quantitative structure-activity relationship analysis of 41 analogs demonstrated that the specific structural substitutions alter their bioactivities. Molecular docking and dynamics simulation analysis indicated the hydrophobic interaction at the FGFR1-D12/D15 interaction was dominant. Evaluation for anti-gastric cancer efficacy of D12 and D15 indicated effective inhibition of cell proliferation, apoptosis induction and cell cycle arrest. Thus, these two FGFR1 inhibitors have therapeutic potential in the treatment of gastric cancer, and this study provides will contribute to the rational design of novel non-ATP competitive FGFR1 inhibitors.
