The potency of heterocyclic curcumin analogues: An evidence-based review

Rodrigues, Fiona Concy; N, Anil Kumar; Thakur, Goutam

doi:10.1016/j.phrs.2021.105489

Cited by 37 publications

(34 citation statements)

References 116 publications

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“…As seen above, curcumin can exhibit a huge range of therapeutic possibilities; however, it presents low solubility and rapid metabolism limiting its absorption in the gastrointestinal tract and resulting in weak bioavailability. The weak bioavailability has been associated to its insolubility in the water and the increased degradation in alkaline solutions or crystallization in acidic environments (69)(70)(71). Significant changes occur in its degradation time according to the pH, at pH> 7 if it degrades in about 30 min, already in acidic conditions, the degradation is much slower, with less than 20% of the total curcumin decomposed in 1 h. When ingested orally, the bioavailability of curcumin can be influenced by the food matrix, like lipids and proteins.…”

Section: Curcuma Longamentioning

confidence: 99%

The Effects of Curcumin on Diabetes Mellitus: A Systematic Review

et al. 2021

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Diabetes mellitus (DM) is an ensemble of metabolic conditions that have reached pandemic proportions worldwide. Pathology’s multifactorial nature makes patient management, including lifelong drug therapy and lifestyle modification, extremely challenging. Currently, there is growing evidence about the effectiveness of using herbal supplements in preventing and controlling DM. Curcumin is a bioactive component found Curcuma longa, which exhibits several physiological and pharmacological properties such as antioxidant, anti-inflammatory, anticancer, neuroprotective, and anti-diabetic activities. For these reasons, our objective is to systematically review the effects of Curcuma longa or curcumin on DM. Databases such as PUBMED and EMBASE were searched, and the final selection included sixteen studies that fulfilled the inclusion criteria. The results showed that curcumin’s anti-diabetic activity might be due to its capacity to suppress oxidative stress and inflammatory process. Also, it significantly reduces fasting blood glucose, glycated hemoglobin, and body mass index. Nanocurcumin is also associated with a significant reduction in triglycerides, VLDL-c, total cholesterol, LDL-c, HDL-c, serum C reactive protein, and plasma malonaldehyde. Therefore, it can be considered in the therapeutic approach of patients with DM.

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Section: Curcuma Longamentioning

confidence: 99%

The Effects of Curcumin on Diabetes Mellitus: A Systematic Review

et al. 2021

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“…Turmeric has been promoted as a therapeutic herb in the majority of indigenous traditional systems, including Ayurveda, Siddha, Unani, and Chinese medicine [ 52 ]. Turmeric’s main active ingredient is curcumin, and its stability and bioavailability are the main issues, so it was modified into semi-synthetic analogs to make it more stable and potentiate its bioactivities [ 17 ]. Some of the curcumin analogues demonstrated superior antiproliferative activity than curcumin not only in the current study, but also in the previous study, where they demonstrated superior antiproliferative activity in single and five dose assays [ 18 , 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Curcumin, one of the active constituents of Curcuma longa L. of the family (Zingiberaceae), has had its structure modified in order to produce biologically active compounds. The chemical modification improved not only the biological activities but also the stability, reducing rotational freedom and minimizing metal-chelation properties [ 17 ]. Curcumin analogues demonstrated broad spectrum activities as anticancer, anti-inflammatory, anti-HIV, anti-Alzheimer’s, antimicrobial, epidermal growth factor receptor (EGFR) inhibitors, and other biological activities as reported in the previous studies [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Engineering of Curcumin, an Active Constituent of Curcuma longa L. (Turmeric) of the Family Zingiberaceae with Improved Antiproliferative Activity

Ali

Tahir³

et al. 2021

Plants

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Cancer is the world’s second leading cause of death, accounting for nearly 10 million deaths and 19.3 million new cases in 2020. Curcumin analogs are gaining popularity as anticancer agents currently. We reported herein the isolation, molecular engineering, molecular docking, antiproliferative, and anti-epidermal growth factor receptor (anti-EGFR) activities of curcumin analogs. Three curcumin analogs were prepared and docked against the epidermal growth factor receptor (EGFR), revealing efficient binding. Antiproliferative activity against 60 NCI cancer cell lines was assessed using National Cancer Institute (NCI US) protocols. The compound 3b,c demonstrated promising antiproliferative activity in single dose (at 10 µM) as well as five dose (0.01, 0.10, 1.00, 10, and 100 µM). Compound 3c inhibited leukemia cancer panel better than other cancer panels with growth inhibition of 50% (GI50) values ranging from 1.48 to 2.73 µM, and the most promising inhibition with GI50 of 1.25 µM was observed against leukemia cell line SR, while the least inhibition was found against non-small lung cancer cell line NCI-H226 with GI50 value of 7.29 µM. Compounds 3b,c demonstrated superior antiproliferative activity than curcumin and gefitinib. In molecular docking, compound 3c had the most significant interaction with four H-bonds and three π–π stacking, and compound 3c was found to moderately inhibit EGFR. The curcumin analogs discovered in this study have the potential to accelerate the anticancer drug discovery program.

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“…Heterocyclic moieties such as isoxazole and pyrazoles have had a great impact in the improvement of the therapeutic potential of natural products and act as ideal scaffolds for natural products in medicinal chemistry (Zhang et al 2018) (Kumar et al 2013) (Naim 2016) (Jain, et al 2006). It is postulated that the β-diketone site is an ideal scaffold for the integration of the heterocyclic moiety and based on previously ordered studies isoxazole, pyrazole and N-phenyl pyrazole and N-amido-pyrazoles are among the most commonly synthesized heterocyclic curcuminoids that have been evaluated for a plethora of activities (Mishra et al 2008) (Sahu 2012) (Ahsan et al 2015) (Sahu et al 2016) (Ahmed 2017) (Rodrigues et al 2021). Such modifications allow for improved stability and bioavailability as compared to curcumin adding to the chance of retention of curcumin-like efficacy.…”

Section: Introductionmentioning

confidence: 99%

The inhibitory potency of isoxazole-curcumin analogue for the management of breast cancer: A comparative in vitro and molecular modeling investigation

Rodrigues

Hari

et al. 2021

Chem. Pap.

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Curcumin, a potent phytochemical derived from the spice element turmeric, has been identified as a herbal remedy decades ago and has displayed promise in the field of medicinal chemistry. However, multiple traits associated with curcumin, such as poor bioavailability and instability, limit its effectiveness to be accepted as a lead drug-like entity. Different reactive sites in its chemical structure have been identified to incorporate modifications as attempts to improving its efficacy. The diketo group present in the center of the structural scaffold has been touted as the group responsible for the instability of curcumin, and substituting it with a heterocyclic ring contributes to improved stability. In this study, four heterocyclic curcumin analogues, representing some broad groups of heterocyclic curcuminoids (isoxazole-, pyrazole-, N-phenyl pyrazole- and N-amido-pyrazole-based), have been synthesized by a simple one-pot synthesis and have been characterized by FTIR, 1H-NMR, 13C-NMR, DSC and LC–MS. To predict its potential anticancer efficacy, the compounds have been analyzed by computational studies via molecular docking for their regulatory role against three key proteins, namely GSK-3β—of which abnormal regulation and expression is associated with cancer; Bcl-2—an apoptosis regulator; and PR which is a key nuclear receptor involved in breast cancer development. One of the compounds, isoxazole-curcumin, has consistently indicated a better docking score than the other tested compounds as well as curcumin. Apart from docking, the compounds have also been profiled for their ADME properties as well as free energy binding calculations. Further, the in vitro cytotoxic evaluation of the analogues was carried out by SRB assay in breast cancer cell line (MCF7), out of which isoxazole-curcumin (IC50–3.97 µM) has displayed a sevenfold superior activity than curcumin (IC50–21.89 µM). In the collation of results, it can be suggested that isoxazole-curcumin behaves as a potential lead owing to its ability to be involved in a regulatory role with multiple significant cancer proteins and hence deserves further investigations in the development of small molecule-based anti-breast cancer agents. Graphic abstract

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The potency of heterocyclic curcumin analogues: An evidence-based review

Cited by 37 publications

References 116 publications

The Effects of Curcumin on Diabetes Mellitus: A Systematic Review

The Effects of Curcumin on Diabetes Mellitus: A Systematic Review

Molecular Engineering of Curcumin, an Active Constituent of Curcuma longa L. (Turmeric) of the Family Zingiberaceae with Improved Antiproliferative Activity

The inhibitory potency of isoxazole-curcumin analogue for the management of breast cancer: A comparative in vitro and molecular modeling investigation

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