Natural chalcones as dual inhibitors of HDACs and NF-κB (original) (raw)
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Chalcones as a Principle Pharmacophore for Design & Development of Novel Anticancer Agents
2016
Chalcones/1,3–diphenyl-2-propene-1-one/benzalacetophenone, are the name of structurally related same compound containing two aromatic rings conjunct via bridge system enveloping carbon and keto-ethylenic moiety, considered to be precursors of bioactive flavonoids and isoflavonoids. The molecule owing to presence of dual aromatic rings and keto-ethylenic functionalities act as a versatile and universally accepted lead for search of candidate drug molecule especially anticancer agents. Lower molecular weight, ease of synthetic modification, single step reaction, high yield of pure products are some of the advantages associated with chalcone making it an attractive target for search of better anticancer drug for future. The paper here, thus discuss some of the aspects of chalcone for development of next generation anticancer agents.
Anticancer Activity of Chalcones and Its Derivatives: Review and In Silico Studies
Molecules
Chalcones are direct precursors in the biosynthesis of flavonoids. They have an α,β-unsaturated carbonyl system which gives them broad biological properties. Among the biological properties exerted by chalcones, their ability to suppress tumors stands out, in addition to their low toxicity. In this perspective, the present work explores the role of natural and synthetic chalcones and their anticancer activity in vitro reported in the last four years from 2019 to 2023. Moreover, we carried out a partial least square (PLS) analysis of the biologic data reported for colon adenocarcinoma lineage HCT-116. Information was obtained from the Web of Science database. Our in silico analysis identified that the presence of polar radicals such as hydroxyl and methoxyl contributed to the anticancer activity of chalcones derivatives. We hope that the data presented in this work will help researchers to develop effective drugs to inhibit colon adenocarcinoma in future works.
The role of chalcones in suppression of NF-κB-mediated inflammation and cancer
International Immunopharmacology, 2011
Although consumption of fruits, vegetables, spices, cereals and pulses has been associated with lower incidence of cancer and other chronic diseases, how these dietary agents and their active ingredients minimize these diseases, is not fully understood. Whether it is oranges, kawa, hops, water-lilly, locorice, wax apple or mulberry, they are all connected by a group of aromatic ketones, called chalcones (1,3-diaryl-2-propen-1-ones). Some of the most significant chalcones identified from these plants include flavokawin, butein, xanthoangelol, 4-hydroxyderricin, cardamonin, 2’,4’-dihydroxychalcone, isoliquiritigenin, isosalipurposide, and naringenin chalcone. These chalcones have been linked with immunomodulation, antibacterial, antifungal, antiviral, anti-inflammatory, antioxidant, anticancer, and antidiabetic activities. The current review, however, deals with the role of various chalcones in inflammation that controls both the immune system and tumorigenesis. Inflammatory pathways have been shown to mediate the survival, proliferation, invasion, angiogenesis and metastasis of tumors. How these chalcones modulate inflammatory pathways, tumorigenesis and immune system is the focus of this review.
Bioorganic & Medicinal Chemistry, 2010
Chalcones have been identified as interesting compounds with cytotoxicity, anti-inflammatory and antioxidant properties. In the present study, simple methoxychalcones were synthesized by Claisen-Schmidt condensation reaction and evaluated for above biological activities. The structures of the compounds were established by IR, 1 H NMR and mass spectral analysis. The data revealed that compound 3s (99-100% at 10 lM concentration) completely inhibit the selected five human cancer cell lines as compared to standard flavopiridol and gemcitabine (70-90% at 700 nM and 500 nM concentrations, respectively), followed by 3a, 3n, 3o, 3p, 3q, 3r. Among the tested compounds 3l, 3m, 3r, and 3s exhibited promising anti-inflammatory activity against TNF-a and IL-6 with 90-100% inhibition at 10 lM concentration.
Advances in Chalcones with Anticancer Activities
Recent Patents on Anti-Cancer Drug Discovery
Chalcones are naturally occurring compounds exhibiting broad spectrum biological activities including anticancer activity through multiple mechanisms. Literature on anticancer chalcones highlights the employment of three pronged strategies, namely; structural manipulation of both aryl rings, replacement of aryl rings with heteroaryl scaffolds, molecular hybridization through conjugation with other pharmacologically interesting scaffolds for enhancement of anticancer properties. Methoxy substitutions on both the aryl rings (A and B) of the chalcones, depending upon their positions in the aryl rings appear to influence anticancer and other activities. Similarly, heterocyclic rings either as ring A or B in chalcones, also influence the anticancer activity shown by this class of compounds. Hybrid chalcones formulated by chemically linking chalcones to other prominent anticancer scaffolds such as pyrrol[2,1-c][1,4]benzodiazepines, benzothiazoles, imidazolones have demonstrated synergistic or additive pharmacological activities. The successful application of these three pronged strategies for discovering novel anticancer agents based on chalcone scaffold has resulted in many novel and chemically diverse chalcones with potential therapeutic application for many types of cancer. This review summarizes the concerted efforts expended on the design and development of anticancer chalcones recorded in recent literature and also provides an overview of the patents published in this area between 2007 and 2014 (WO2013022951, WO201201745 & US2012029489).
Antimitotic and Antiproliferative Activities of Chalcones: Forward Structure–Activity Relationship
Journal of Medicinal Chemistry, 2008
A series of 59 chalcones was prepared and evaluated for the antimitotic effect against K562 leukemia cells. The most active chalcones were evaluated for their antiproliferative activity against a panel of 11 human and murine cell cancer lines. We found that three chalcones were of great interest as potential antimitotic drugs. In vivo safety studies conducted on one of the most active chalcones revealed that the compound was safe, allowing further in vivo antitumor evaluation.
Biological Role of Chalcones in Medicinal Chemistry
Vector-Borne Diseases: Recent Developments in Epidemiology and Control [Working Title]
Chalcones are promising synthons and bioactive scaffolds of great medicinal interest due to their numerous pharmacological and biological activities. They are well recognized to possess antimicrobial, anticancer, antitubercular, antioxidant, anti-inflammatory, antileishmanial, and other significant biological activities. This chapter highlights recent updates and applications of chalcones as biologically, pharmacologically, and medicinally important entities.
In vitro evaluation of newly developed chalcone analogues in human cancer cells
Cancer chemotherapy …, 2000
Purpose: Among¯avonoids, chalcones have been identi®ed as interesting compounds having chemopreventive and antitumor properties. We studied a panel of newly developed chalcone analogues (S1±S10) using MDA-MB 231 and MCF-7 ADRr breast cancer cells and the T-leukemic Jurkat cell line. Quercetin was used as the reference compound. Methods: Antiproliferative activity was evaluated by cell counts performed after 72 h of exposure to the drugs. DNA analysis and redox activity were evaluated using¯ow cytometry. Apoptosis was assessed by morphological analysis, using YOYO-1 as DNA dye; p-glycoprotein function was ascertained by quantitating the eux of rhodamine 123. Results: All cells were sensitive to chalcone analogues yielding IC 50 in micromolar concentrations with the following order regardless of the multidrug resistance (MDR) status: S1 > S2 > quercetin. S1 and S2, the most active compounds, were selected to evaluate their eect on the cell cycle, apoptosis, redox activity, and modulation of the p-glycoprotein function. No signi®cant perturbation in cell cycle was seen with concentration up to 1 lM after 24 h. After 72 h a slight increase in G 2 /M block and DNA fragmentation occurred at 10 lM. Morphological analysis of apoptosis showed that chalcone analogues induced apoptosis to a higher extent than quercetin. Redox analysis demonstrated that all substances were able to increase intracellular thiol levels, which returned to baseline value after 24 h for all drugs except quercetin. Production of reactive oxygen species was essentially unaected by all compounds. Finally, in MDR-positive MCF-7 ADRr cells chalcone analogues were unable to modulate p-glycoprotein function while quercetin was able to. Conclusions: Newly developed S1 and S2 chalcones have a dierent but higher antitumor activity than quercetin and could be considered as potential new anticancer drugs.