Curcumin has been reported to possess multifunctional bioactivities with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. Up to...Curcumin has been reported to possess multifunctional bioactivities with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. Up to now, multiple approaches are being sought to overcome these limitations to obtaining “super curcumin”, and many analogues of curcumin have been designed and synthesized. In all of those analogues, a series of mono-carbonyl curcumin analogues deleting the β-diketone draw our attention. Since the seven-carbon β-diketone linker in curcumin may be responsible for its instability, the series of mono-carbonyl curcumin analogues deleting the β-diketone may be potential prodrug with improved pharmacokinetic and pharmacodynamic properties. This review just focuses on these more stable mono-carbonyl analogues of curcumin, and shows the new class of active structure by introducing the synthesis and anticancer activity of them.展开更多
Five novel curcumin analogues bearing different substituents at 4-position of phenyl group were synthesized. Their structures were confirmed by NMR and HRMS spectrum. Their cytotoxic activities against six tumor cell ...Five novel curcumin analogues bearing different substituents at 4-position of phenyl group were synthesized. Their structures were confirmed by NMR and HRMS spectrum. Their cytotoxic activities against six tumor cell lines were tested by the standard MTT assay in vitro. The results indicated that four analogues （1A-1C, 1E） with solubilizing moieties showed selective potent cytotoxicity against HepG2, HeLa and CT26 cell lines, and analogue 1A and 1C exhibited more potent cytotoxicity than curcumin against CT26 cell line. It was suggested that introduction of appropriate substituents to 4-position of phenyl group might be a potential option for structural modification of curcumin.展开更多
Objective: To identify commonly regulated genes in HPV-infected He La and Ca Ski cervical cancer cells treated with curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17) and to explore potential mechan...Objective: To identify commonly regulated genes in HPV-infected He La and Ca Ski cervical cancer cells treated with curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17) and to explore potential mechanisms that underlie its cytotoxic, anti-proliferative and apoptotic activity. Methods: He La and Ca Ski cells were treated with 2×EC50 and 3×EC50 doses of MS17 for 24 h and the RNA extracts were subjected to one-colour microarray-based gene expression profiling. Pair-wise significant genes(false discovery rate-corrected, P<0.05) were analysed for fold change(FC) compared to control samples. Differentially expressed genes with FC≥2.0(up-regulated; FC≥2.0 and down-regulated; FC≤-2.0) compared to the control samples were filtered through and analysed to create a global gene expression profile. Mutually regulated genes were ranked by FC and categorised by gene ontology. Results: Our data indicated dose-dependent regulation by MS17 and identified top 20 mutually upand down-regulated genes each in He La and Ca Ski cells. Amongst these 17 were commonly regulated in both cell lines. These include the up-regulation of CCL26, DEFB103 B, IL1 RL1, LY96, GCNT3, MMP10, MMP3, GADD45 G and HSPA6, and the down-regulation of TENM2, NEBL, KIFC1, CTDSP1, IGFBP5, LTBP1, NREP and MXD3. These genes were associated with key biological functions that were proposed to mediate the anticancer activity of MS17 in cervical cancer cells such as immune response, metabolic processes, proteolysis, programmed cell death, unfolded protein response, cell adhesion, cytoskeletal organisation, phosphatase activity, signal transduction and transcription regulator activity. Conclusions: Identification of seventeen common genes modulated by MS17 could be used as potential therapeutic targets in both cervical cancer cell lines and the findings of this study could be used to present an insight into the potential antitumor activity of MS17 in cervical cancer.展开更多
Two monocarbonyl analogs of curcumin containing bis（2,6-difluorobenzyl） were synthesized,and their molecular structures were characterized by 1H NMR,ESI-MS,and X-ray crystallography.In this paper,the crystal structu...Two monocarbonyl analogs of curcumin containing bis（2,6-difluorobenzyl） were synthesized,and their molecular structures were characterized by 1H NMR,ESI-MS,and X-ray crystallography.In this paper,the crystal structures of these two analogs（A75 and C75） are described and compared with their bis（2-fluorobenzyl） analogues as well as with the available data of curcumin.The cyclopentane rings in A75 have an envelope conformation,while the cyclohexane ring in C75 has a chair conformation.The compounds are symmetrical and the central structure of A75 and C75 connects with two benzylidene rings through E,E-oriented double bonding.展开更多
The global incidence of oral cancer has steadily increased in recent years and is associated with high morbidity and mortality.Oral cancer is the most common cancer in the head and neck region,and is predominantly of ...The global incidence of oral cancer has steadily increased in recent years and is associated with high morbidity and mortality.Oral cancer is the most common cancer in the head and neck region,and is predominantly of epithelial origin(i.e.squamous cell carcinoma).Oral cancer treatment modalities mainly include surgery with or without radiotherapy and chemotherapy.Though proven effective,chemotherapy has significant adverse effects with possibilities of tumor resistance to anticancer drugs and recurrence.Thus,there is an imperative need to identify suitable anticancer therapies that are highly precise with minimal side effects and to make oral cancer treatment effective and safer.Among the available adjuvant therapies is curcumin,a plant polyphenol isolated from the rhizome of the turmeric plant Curcuma longa.Curcumin has been demonstrated to have antiinfectious,antioxidant,anti-inflammatory,and anticarcinogenic properties.Curcumin has poor bioavailability,which has been overcome by its various analogues and nanoformulations,such as nanoparticles,liposome complexes,micelles,and phospholipid complexes.Studies have shown that the anticancer effects of curcumin are mediated by its action on multiple molecular targets,including activator protein 1,protein kinase B(Akt),nuclear factorκ-light-chainenhancer of activated B cells,mitogen-activated protein kinase,epidermal growth factor receptor(EGFR)expression,and EGFR downstream signaling pathways.These targets play important roles in oral cancer pathogenesis,thereby making curcumin a promising adjuvant treatment modality.This review aims to summarize the different novel formulations of curcumin and their role in the treatment of oral cancer.展开更多
Cancer of the prostate gland is a leading cause of death. In the present study, we studied the effects and mechanisms of curcumin analogue E10, docetaxel or their combination on prostate cancer （PC）-3 cells. Treatme...Cancer of the prostate gland is a leading cause of death. In the present study, we studied the effects and mechanisms of curcumin analogue E10, docetaxel or their combination on prostate cancer （PC）-3 cells. Treatment of PC-3 cells with El0 or docetaxel resulted in growth inhibition in a concentration-reliant fashion. Combinations of E10 and docetaxel inhibited the growth of PC-3 cells in a synergistic manner. Effects of a combination of E10 and docetaxel were associated with synergistic inhibition of the transcriptional activity of nuclear factor-kappa B （NF-KB）, and robust reductions in the levels of B-cell lymphoma-2 （Bcl-2） were found in PC-3 cells treated with a combination of E10 and docetaxel. Our data indicated that the effects of El0 in combination with docetaxel on PC-3 cells were associated with inhibition of NF-r,B and Bcl-2. Further studies using suitable animal models are necessary to determine the in vivo effect of this combination.展开更多
在B3LYP/6-31G(d,p)水平下优化了四种姜黄素类似物的几何构型,并通过振动分析验证了其构型稳定性。在B3LYP/6-311G(d,p)水平下计算了该类化合物的核磁共振谱,研究结果表明:四种化合物主体结构共平面性较好,为一较大共轭体系。由于羟基...在B3LYP/6-31G(d,p)水平下优化了四种姜黄素类似物的几何构型,并通过振动分析验证了其构型稳定性。在B3LYP/6-311G(d,p)水平下计算了该类化合物的核磁共振谱,研究结果表明:四种化合物主体结构共平面性较好,为一较大共轭体系。由于羟基及甲氧基的引入,使Compound-B/C/D中C3,C4以及Compound-A/D中C5均具有较大δ值,Compound-A中C4和C6的δ值相对较小,C3的δ值相对较大。而在羰基与碳碳双键所形成的共轭羰基化合物中,羰基C13的δ值(183ppm)相对于乙醛中的δ值(201ppm)有所减小,C11,15(α碳)的δ值(122ppm)相对减小,而C9,17(β碳)的δ值(145ppm)相对增大。最后,通过线性回归方法,利用相关系数值r研究了1 H NMRδ值的实验和理论计算值的相关性,结果表明相关性较好,实验值和理论值基本吻合。展开更多
文摘Curcumin has been reported to possess multifunctional bioactivities with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. Up to now, multiple approaches are being sought to overcome these limitations to obtaining “super curcumin”, and many analogues of curcumin have been designed and synthesized. In all of those analogues, a series of mono-carbonyl curcumin analogues deleting the β-diketone draw our attention. Since the seven-carbon β-diketone linker in curcumin may be responsible for its instability, the series of mono-carbonyl curcumin analogues deleting the β-diketone may be potential prodrug with improved pharmacokinetic and pharmacodynamic properties. This review just focuses on these more stable mono-carbonyl analogues of curcumin, and shows the new class of active structure by introducing the synthesis and anticancer activity of them.
文摘Five novel curcumin analogues bearing different substituents at 4-position of phenyl group were synthesized. Their structures were confirmed by NMR and HRMS spectrum. Their cytotoxic activities against six tumor cell lines were tested by the standard MTT assay in vitro. The results indicated that four analogues （1A-1C, 1E） with solubilizing moieties showed selective potent cytotoxicity against HepG2, HeLa and CT26 cell lines, and analogue 1A and 1C exhibited more potent cytotoxicity than curcumin against CT26 cell line. It was suggested that introduction of appropriate substituents to 4-position of phenyl group might be a potential option for structural modification of curcumin.
基金financially supported by the Fundamental Research Grant Scheme(No.FRGS/1/2013/SKK01/MUSM/02/1)under the Ministry of Higher Education,Malaysia
文摘Objective: To identify commonly regulated genes in HPV-infected He La and Ca Ski cervical cancer cells treated with curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17) and to explore potential mechanisms that underlie its cytotoxic, anti-proliferative and apoptotic activity. Methods: He La and Ca Ski cells were treated with 2×EC50 and 3×EC50 doses of MS17 for 24 h and the RNA extracts were subjected to one-colour microarray-based gene expression profiling. Pair-wise significant genes(false discovery rate-corrected, P<0.05) were analysed for fold change(FC) compared to control samples. Differentially expressed genes with FC≥2.0(up-regulated; FC≥2.0 and down-regulated; FC≤-2.0) compared to the control samples were filtered through and analysed to create a global gene expression profile. Mutually regulated genes were ranked by FC and categorised by gene ontology. Results: Our data indicated dose-dependent regulation by MS17 and identified top 20 mutually upand down-regulated genes each in He La and Ca Ski cells. Amongst these 17 were commonly regulated in both cell lines. These include the up-regulation of CCL26, DEFB103 B, IL1 RL1, LY96, GCNT3, MMP10, MMP3, GADD45 G and HSPA6, and the down-regulation of TENM2, NEBL, KIFC1, CTDSP1, IGFBP5, LTBP1, NREP and MXD3. These genes were associated with key biological functions that were proposed to mediate the anticancer activity of MS17 in cervical cancer cells such as immune response, metabolic processes, proteolysis, programmed cell death, unfolded protein response, cell adhesion, cytoskeletal organisation, phosphatase activity, signal transduction and transcription regulator activity. Conclusions: Identification of seventeen common genes modulated by MS17 could be used as potential therapeutic targets in both cervical cancer cell lines and the findings of this study could be used to present an insight into the potential antitumor activity of MS17 in cervical cancer.
基金supported by the National Natural Science Foundation of China (21102106)Project of Wenzhou Sci&Tech Bureau (Y20100273 and Y20100006)Natural Science Foundation of Zhejiang Province (Y4110197 and Y2101108)
文摘Two monocarbonyl analogs of curcumin containing bis（2,6-difluorobenzyl） were synthesized,and their molecular structures were characterized by 1H NMR,ESI-MS,and X-ray crystallography.In this paper,the crystal structures of these two analogs（A75 and C75） are described and compared with their bis（2-fluorobenzyl） analogues as well as with the available data of curcumin.The cyclopentane rings in A75 have an envelope conformation,while the cyclohexane ring in C75 has a chair conformation.The compounds are symmetrical and the central structure of A75 and C75 connects with two benzylidene rings through E,E-oriented double bonding.
文摘The global incidence of oral cancer has steadily increased in recent years and is associated with high morbidity and mortality.Oral cancer is the most common cancer in the head and neck region,and is predominantly of epithelial origin(i.e.squamous cell carcinoma).Oral cancer treatment modalities mainly include surgery with or without radiotherapy and chemotherapy.Though proven effective,chemotherapy has significant adverse effects with possibilities of tumor resistance to anticancer drugs and recurrence.Thus,there is an imperative need to identify suitable anticancer therapies that are highly precise with minimal side effects and to make oral cancer treatment effective and safer.Among the available adjuvant therapies is curcumin,a plant polyphenol isolated from the rhizome of the turmeric plant Curcuma longa.Curcumin has been demonstrated to have antiinfectious,antioxidant,anti-inflammatory,and anticarcinogenic properties.Curcumin has poor bioavailability,which has been overcome by its various analogues and nanoformulations,such as nanoparticles,liposome complexes,micelles,and phospholipid complexes.Studies have shown that the anticancer effects of curcumin are mediated by its action on multiple molecular targets,including activator protein 1,protein kinase B(Akt),nuclear factorκ-light-chainenhancer of activated B cells,mitogen-activated protein kinase,epidermal growth factor receptor(EGFR)expression,and EGFR downstream signaling pathways.These targets play important roles in oral cancer pathogenesis,thereby making curcumin a promising adjuvant treatment modality.This review aims to summarize the different novel formulations of curcumin and their role in the treatment of oral cancer.
基金The National Cancer Institute of China(Grant No.P30-CA072720)the National Natural Science Foundation of China(Gr ant No.81272452)the PhD Start-up Fund of Natural Science Foundation of Guangdong Province,China(Grant No.2014A030310329)
文摘Cancer of the prostate gland is a leading cause of death. In the present study, we studied the effects and mechanisms of curcumin analogue E10, docetaxel or their combination on prostate cancer （PC）-3 cells. Treatment of PC-3 cells with El0 or docetaxel resulted in growth inhibition in a concentration-reliant fashion. Combinations of E10 and docetaxel inhibited the growth of PC-3 cells in a synergistic manner. Effects of a combination of E10 and docetaxel were associated with synergistic inhibition of the transcriptional activity of nuclear factor-kappa B （NF-KB）, and robust reductions in the levels of B-cell lymphoma-2 （Bcl-2） were found in PC-3 cells treated with a combination of E10 and docetaxel. Our data indicated that the effects of El0 in combination with docetaxel on PC-3 cells were associated with inhibition of NF-r,B and Bcl-2. Further studies using suitable animal models are necessary to determine the in vivo effect of this combination.
文摘在B3LYP/6-31G(d,p)水平下优化了四种姜黄素类似物的几何构型,并通过振动分析验证了其构型稳定性。在B3LYP/6-311G(d,p)水平下计算了该类化合物的核磁共振谱,研究结果表明:四种化合物主体结构共平面性较好,为一较大共轭体系。由于羟基及甲氧基的引入,使Compound-B/C/D中C3,C4以及Compound-A/D中C5均具有较大δ值,Compound-A中C4和C6的δ值相对较小,C3的δ值相对较大。而在羰基与碳碳双键所形成的共轭羰基化合物中,羰基C13的δ值(183ppm)相对于乙醛中的δ值(201ppm)有所减小,C11,15(α碳)的δ值(122ppm)相对减小,而C9,17(β碳)的δ值(145ppm)相对增大。最后,通过线性回归方法,利用相关系数值r研究了1 H NMRδ值的实验和理论计算值的相关性,结果表明相关性较好,实验值和理论值基本吻合。
