Stable and Potent Analogues Derived from the Modification of the Dicarbonyl Moiety of Curcumin

Chakraborti, Soumyananda; Dhar, Gopa; Dwivedi, Vishnu; Das, Amlan; Poddar, Asim; Chakraborti, Gopal; Basu, Gautam; Chakrabarti, Pinak; Surolia, Avadhesha; Bhattacharyya, Bhabatarak

doi:10.1021/bi400734e

Cited by 64 publications

(42 citation statements)

References 45 publications

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“…Curcumin can exist as a tautomeric mixture of keto and enol forms in solutions, and the enol form was found to be responsible for the rapid degradation of the curcumin. Chakraborti et al., found that the stability of curcumin was improved when the central diketone moiety of the curcumin was replaced by isooxazole and pyrazole groups. Structural modifications of curcumin were proven to be a meaningful approach to discover analogues with enhanced properties .…”

Section: Methodsmentioning

confidence: 99%

Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms

et al. 2017

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Curcumin is a popular, plant-derived compound that has been extensively investigated for diverse range of biological activities. Anticancer activity against various types of cancers and high-safety profile associated with curcumin makes it very attractive. In this study, we report the synthesis and evaluation of pyrazole and click chemistry curcumin analogues for Head and Neck cancer. MTT assay against head and neck cancer cell lines CAL27 and UM-SCC-74A revealed the micromolar potency of the synthesized compounds. To determine the possible molecular mechanisms, effect of these analogues in the expression of pSTAT3, pFAK, pERK1/2 and pAKT was studied. Interestingly, compounds 2 and 5 significantly inhibited the pSTAT3 (Tyr 705) phosphorylation. As far as other compounds, they showed potent cytotoxicity against CAL27; however, these compounds did not show any activity on pSTAT3 phosphorylation at IC 50 concentration level. Molecular docking studies revealed the possible binding mode of pyrazole compound 2 in the SH2 domain of STAT3. K E Y W O R D Sclick chemistry curcumin analogue, curcumin, head and neck squamous cell carcinoma, pyrazole analogue Curcumin, a natural polyphenol which is used as a food colourant, and herbal medicine in Asia. Curcumin has received a lot of attention recently due to its high-safety profile and efficacy in treating various diseases.[1-3] Potential anticancer activities associated with curcumin make it a promising therapeutic agent. Apart from anticancer activity, it has shown antioxidant, anti-inflammatory, chemopreventive, chemotherapeutic, antimicrobial and antifungal activities. Curcumin (Figure 1) is being vigorously studied for its effect against breast cancer, prostate cancer, liver cancer, ovarian cancer and cervical cancer.[4] It demonstrated cytotoxic effects against cancer cell lines and cytoprotective effects on non-cancer cells. One of the important aspects of curcumin is its high-safety profile of up to 12 g per day oral administration.[5]Nevertheless, there are a number of challenges, low aqueous solubility, poor absorption and rapid metabolism that limits its therapeutic efficacy.[6] Curcumin can exist as a tautomeric mixture of keto and enol forms in solutions, and the enol form was found to be responsible for the rapid degradation of the curcumin. Chakraborti et al., [7] found that the stability of curcumin was improved when the central diketone moiety of the curcumin was replaced by isooxazole and pyrazole groups. Structural modifications of curcumin were proven to be a meaningful approach to discover analogues with enhanced properties. [8][9][10][11][12] Conjugates of curcumin with β-and γ-cyclodextrin, liposomal and loaded nanoparticles and nanoemulsion are some of the lipid-based colloidal system that has been employed to enhance water solubility and improving its bioavailability.[13] Recent work supports the

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Section: Methodsmentioning

confidence: 99%

Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms

et al. 2017

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“…Interestingly, compounds 2 and 3 also showed better free radical scavenging activity than curcumin ( Table 4). [58] Ahsan et al (2013) depicted synthesis, characterization and in vitro anticancer activity of a novel series of curcumin analogs to explore potential therapeutics for cancer. Several compounds were tested and showed promising anticancer activity in both onedose and 5-dose assays.…”

Section: Curcumin Pyrazole and Isoxazole Analogs As Anticancer Agentsmentioning

confidence: 99%

Recent Updates in Curcumin Pyrazole and Isoxazole Derivatives: Synthesis and Biological Application

Patel

Halpani

2019

Chemistry & Biodiversity

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Curcumin is an admired, plant-derived compound that has been extensively investigated for diverse range of biological activities, but the use of this polyphenol is limited due to its instability. Chemical modifications in curcumin are reported to seize this limitation; such efforts are intensively performed to discover molecules with similar but improved stability and better properties. Focal points of these reviews are synthesis of stable pyrazole and isoxazole analogs of curcumin and application in various biological systems. This review aims to emphasize the latest evidence of curcumin pyrazole analogs as a privileged scaffold in medicinal chemistry. Manifold features of curcumin pyrazole analogs will be summarized herein, including the synthesis of novel curcumin pyrazole analogs and the evaluation of their biological properties. This review is expected to be a complete, trustworthy and critical review of the curcumin pyrazole analogs template to the medicinal chemistry community.

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“…Curcumin is a naturally occurring phenol found in turmeric spice. A highly lipophilic molecule, curcumin exists in 1,3-diketo and two enol tautomers, and displays relatively low bioavailability due to degradation of the enol tautomer and rapid excretion from the body (133,134). Many strategies have been attempted to increase curcumin bioavailability, including nanoparticulate formulations, synthesis of curcumin analogues, co-treatment with piperine (a UDP-glucuronosyl transferase inhibitor), and packaging in micelles (133,(135)(136)(137)(138).…”

Section: Natural Compounds 521 Curcuminmentioning

confidence: 99%

Molecular strategies for modulating Wnt signaling

et al. 2017

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The importance of the Wnt signaling cascade in the fields of developmental biology, regenerative medicine, cancer genetics, and neurobiology has fueled a wide search for potent pharmacological agents capable of controlling Wnt signaling. Numerous fields of study have lent assistance to this endeavor, yielding both natural and synthetic compounds that are capable of inducing or inhibiting Wnt at multiple stages within the pathway. Further, there is a large of body research which has investigated endogenous Wnt inducers and inhibitors, namely the secreted Wnts, Dickkof proteins, secreted Frizzled-Related Proteins, and Wnt Inhibitory Factor-1, along with others which may act via indirect means to stimulate or inhibit Wnt (e.g. the Smads, bone morphogenetic proteins, and Hedgehog proteins). This review will summarize the research surrounding currently available small molecules used to target Wnt signaling. These compounds will be classified based upon their ability to stimulate or inhibit Wnt, their derivation (natural or synthetic), and their specific mechanism of action.

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Stable and Potent Analogues Derived from the Modification of the Dicarbonyl Moiety of Curcumin

Cited by 64 publications

References 45 publications

Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms

Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms

Recent Updates in Curcumin Pyrazole and Isoxazole Derivatives: Synthesis and Biological Application

Molecular strategies for modulating Wnt signaling

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