Synthesis and evaluation of curcumin analogues as potential thioredoxin reductase inhibitors

Xu, Qiong; Zhong, Liu; Shao, Weiwei; Liu, Xing; Jing, Da-Ping; Yu, Yong; An, Lin‐Kun; Huang, Shi‐Liang; Bu, Xianzhang; Huang, Zhi‐Shu; Gu, Lian‐Quan

doi:10.1016/j.bmc.2008.07.054

Cited by 59 publications

(28 citation statements)

References 30 publications

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“…[13][14][15] Several approaches to enhance the water solubility, chemical stability, and resultant bioavailability of curcumin have been investigated. [16][17][18][19][20][21][22][23][24][25][26][27][28] Adding adjuvants such as piperine, which can inhibit glucuronidation metabolic pathways of curcumin, has been used to improve curcumin bioavailability. 16 Development of curcumin formulations as nanoparticles, liposomes, micelles, and phospholipid complexes is an alternative approach to prolong half-life, improve membrane permeability, and increase the metabolic stability of curcumin.…”

Section: Introductionmentioning

confidence: 99%

“…[17][18][19][20][21] A chemical modification approach has been used to generate curcumin derivatives with increased biological activity and improved pharmacokinetic properties. [22][23][24][25][26][27][28] For example, Qiu et al 26 synthesized a series of curcumin derivatives by replacing a phenyl ring with furan, and these compounds have higher inhibitory potency than curcumin against growth of several thioredoxin reductase-overexpressing cancer cell lines in vitro. Ferrari et al 27 synthesized glycosylated curcumin analogues with increased water solubility and improved stability, which resulted in higher cytotoxicity against a cisplatin-resistant human ovarian carcinoma cell line.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Different Carboxylic Ester Spacers on Chemical Stability, Release Characteristics, and Anticancer Activity of Mono-PEGylated Curcumin Conjugates

Wichitnithad

Nimmannit

Callery

et al. 2011

Journal of Pharmaceutical Sciences

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Different Carboxylic Ester Spacers on Chemical Stability, Release Characteristics, and Anticancer Activity of Mono-PEGylated Curcumin Conjugates

Wichitnithad

Nimmannit

Callery

et al. 2011

Journal of Pharmaceutical Sciences

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“…Following the observation that curcumin inhibits rat thioredoxin reductase [91], a number of analogs of this naturally occurring compound have been evaluated, including 65a and 65b [92]. The IC 50 values of 61a and 61b towards thioredoxin reductase are 24.9 and 5.1 μM, respectively, and this mechanism of action may contribute to the antineoplastic properties of some or all conjugated dienones.…”

Section: Modes Of Actionmentioning

confidence: 99%

1,5-Diaryl-3-oxo-1,4-pentadienes: A Case for Antineoplastics with Multiple Targets

Das

Sharma²,

Dimmock³

2009

CMC

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A number of organic molecules which contain the 1,5-diaryl-3-oxo-1,4-pentadienyl group, referred to hereafter as the dienone moiety, have antineoplastic properties. Emphasis is made on the attachment of this structural moiety to several molecular scaffolds, namely piperidines, Nacylpiperidines, cycloalkanes and 3,4-dihydro-1H-napthalenes. Many of these compounds are potent cytotoxins having micromolar and nanomolar IC 50 values towards a wide range of neoplastic and transformed cells. On occasions, greater toxicity towards neoplasms than normal cells has been demonstrated. A number of these compounds have in vivo anticancer properties and in general excellent tolerability in rodents is demonstrated. The way in which a number of physicochemical properties such as redox potentials, torsion angles, atomic charges and logP values govern cytotoxic potencies are presented. The importance of the shapes of different compounds as determined by molecular modeling in contributing to antineoplastic properties is outlined. Arguments are presented in favour of designing antineoplastics which have multiple sites of action in contrast to those bioactive molecules which have only one molecular target. A number of compounds which possess the dienone group have different modes of action some of which are chronicled in this review, such as inducing apoptosis, affecting respiration in mitochondria, inhibiting macro-molecular biosynthesis and both inhibiting and stimulating certain enzymes. Other important properties of these compounds are discussed including their anti-angiogenic, MDR-revertant and antioxidant properties. It is hoped that this eulogy of the importance of the dienone group will encourage researchers to consider incorporating this structural unit into candidate cytotoxins in the future.

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“…The studies also indicated down-regulation of Bcl-2 protein and activation of caspase-3 in the apoptotic death of tumor cells. Qui et al [56] have synthesized a series of curcumin derivatives with modifications in the aryl ring and have evaluated their inhibitory activities on thioredoxin reductase (TrxR) by DTNB assay in vitro. Most of the analogs were found to inhibit TrxR in the low micromolar range.…”

Section: Modifications Of Aryl Sidementioning

confidence: 99%

Perspectives on New Synthetic Curcumin Analogs and their Potential Anticancer Properties

Vyas¹,

Dandawate²,

Padhyé³

et al. 2013

Current Pharmaceutical Design

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Curcumin is the active component of dried rhizome of Curcuma longa, a perennial herb belonging to ginger family, cultivated extensively in south and southeastern tropical Asia. It is widely consumed in the Indian subcontinent, south Asia and Japan in traditional food recipes. Extensive research over last few decades has shown that curcumin is a potent anti-inflammatory agent with powerful therapeutic potential against a variety of cancers. It suppresses proliferation and metastasis of human tumors through regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases and other enzymes. It induces apoptotic cell death and also inhibits proliferation of cancer cells by cell cycle arrest. Pharmacokinetic data has shown that curcumin undergoes rapid metabolism leading to glucuronidation and sulfation in the liver and excretion in the feces, which accounts for its poor systemic bioavailability. The compound has, therefore, been formulated and administered using different drug delivery systems such as liposomes, micelles, polysaccharides, phospholipid complexes and nanoparticles that can overcome the limitation of bioavailability to some extent. Attempts to avoid rapid metabolism of curcumin until now have been met with limited success. This has prompted researchers to look for new synthetic curcumin analogs in order to overcome the drawbacks of limited bioavailability and rapid metabolism, and gain efficacy with reduced toxicity. In this review we provide a summarized account of novel synthetic curcumin formulations and analogs, and the recent progress in the field of cancer prevention and treatment.

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Synthesis and evaluation of curcumin analogues as potential thioredoxin reductase inhibitors

Cited by 59 publications

References 30 publications

Effects of Different Carboxylic Ester Spacers on Chemical Stability, Release Characteristics, and Anticancer Activity of Mono-PEGylated Curcumin Conjugates

Effects of Different Carboxylic Ester Spacers on Chemical Stability, Release Characteristics, and Anticancer Activity of Mono-PEGylated Curcumin Conjugates

1,5-Diaryl-3-oxo-1,4-pentadienes: A Case for Antineoplastics with Multiple Targets

Perspectives on New Synthetic Curcumin Analogs and their Potential Anticancer Properties

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