Synthesis of some coumarinyl chalcones and their antiproliferative activity against breast cancer cell lines
01 May 2011-Letters in Drug Design & Discovery (Bentham Science Publishers)-Vol. 8, Iss: 4, pp 308-311
TL;DR: One of the compound 3i bearing methoxy substitutions at the R1, R2 and R3 positions of the phenyl ring showed comparable potency to the reference drug cisplatin as well as a two-fold higher selectivity for the breast cancer cell lines than 184B5 cells.
Abstract: A series of coumarinyl chalcones derivatives were synthesized and evaluated for their antiproliferative activities on three different breast cancer cell lines (MDA-MB231, MDA-MB468, MCF7) and one non-cancer breast epithelial cell line (184B5). The coumarinyl derivatives exhibited anticancer activity against breast cancer cell lines at a micromolar range. A structure-activity relationship (SAR) analysis was performed by studying the effect of substituents on their antiproliferative activities. One of the compound 3i bearing methoxy substitutions at the R1, R2 and R3 positions of the phenyl ring showed comparable potency to the reference drug cisplatin as well as a two-fold higher selectivity for the breast cancer cell lines than 184B5 cells.
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TL;DR: This review summarizes the concerted efforts expended on the design and development of anticancer chalcones recorded in recent literature and provides an overview of the patents published in this area between 2007 and 2014.
Abstract: 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).
175 citations
TL;DR: The present mini review provides a systematic summary on natural and synthetic agents of coumarin–chalcone hybrids on the basis of their therapeutic properties to assist medicinal chemists in the effective and successful development of Coumarin-Chalcone hybrids.
Abstract: Naturally and synthetically derived hybrid molecules are an attractive source for therapeutic agent development due to their dual or multiple modes of action and other advantages. Coumarin and chalcone, two important classes of natural products affording diverse pharmacological activities, make themselves ideal blocks for building a coumarin–chalcone hybrid scaffold as a bioactive agent. Provoked by the promising medicinal application of such hybrids, the scientific community has reported dozens of coumarin–chalcone hybrids with a wide spectrum of biological properties including anticancer, antimicrobial, antimalarial, antioxidant, antitubercular and so on, through synthetic hybridization strategy or characterization from natural sources. The present mini review provides a systematic summary on natural and synthetic agents of coumarin–chalcone hybrids on the basis of their therapeutic properties. It is expected to assist medicinal chemists in the effective and successful development of coumarin–chalcone hybrids.
73 citations
16 Jun 2021
TL;DR: Chalcones (1,3-diaryl-2-propen-1-ones) are precursors for flavonoids and isoflavonoids, which are common simple chemical scaffolds found in many naturally occurring compounds as discussed by the authors.
Abstract: Chalcones (1,3-diaryl-2-propen-1-ones) are precursors for flavonoids and isoflavonoids, which are common simple chemical scaffolds found in many naturally occurring compounds. Many chalcone derivatives were also prepared due to their convenient synthesis. Chalcones as weandhetic analogues have attracted much interest due to their broad biological activities with clinical potentials against various diseases, particularly for antitumor activity. The chalcone family has demonstrated potential in vitro and in vivo activity against cancers via multiple mechanisms, including cell cycle disruption, autophagy regulation, apoptosis induction, and immunomodulatory and inflammatory mediators. It represents a promising strategy to develop chalcones as novel anticancer agents. In addition, the combination of chalcones and other therapies is expected to be an effective way to improve anticancer therapeutic efficacy. However, despite the encouraging results for their response to cancers observed in clinical studies, a full description of toxicity is required for their clinical use as safe drugs for the treatment of cancer. In this review, we will summarize the recent advances of the chalcone family as potential anticancer agents and the mechanisms of action. Besides, future applications and scope of the chalcone family toward the treatment and prevention of cancer are brought out.
73 citations
TL;DR: Hybridization of chalcone moiety with other anticancer pharmacophores could provide the hybrids which have the potential to overcome drug resistance and improve the specificity, so it represents a promising strategy to develop novel anticancer agents.
Abstract: The continuous emergency of drug-resistant cancers and the low specificity of anticancer agents have been the major challenges in the control and treatment of cancer, making an urgent need to develop novel anticancer agents with high efficacy. Chalcones, precursors of flavonoids and isoflavonoids, exhibit structural heterogeneity and can act on various drug targets. Chalcones which demonstrated potential in vitro and in vivo activity against both drug-susceptible and drug-resistant cancers, are useful templates for the development of novel anticancer agents. Hybridization of chalcone moiety with other anticancer pharmacophores could provide the hybrids which have the potential to overcome drug resistance and improve the specificity, so it represents a promising strategy to develop novel anticancer agents. This review emphasizes the development, the mechanisms of action as well as structure-activity relationships of chalcone hybrids with potential therapeutic application for many cancers in recent 10 years.
62 citations
TL;DR: An overview of the design strategies employed by various scientists over the past 20 years in the synthesis of different chemical structure-based anticancer hybrids using molecular hybridization techniques is presented.
Abstract: Nowadays, hybrid drugs containing two or more covalently linked known potential pharmacophores are designed to simultaneously modulate multiple targets of multifactorial diseases to overcome the side effects associated with a single drug. In this review, an overview of the design strategies employed by various scientists over the past 20 years has been presented. The overview includes the synthesis of different chemical structure-based anticancer hybrids using molecular hybridization techniques. To tackle one of the world's most devastating diseases such as cancer, researchers have exploited the molecular hybridization (MH) technique to synthesize different anticancer hybrids, which include hybrids based on azole, camptothecin, chalcone, pyrrolobenzodiazepine (PBD), coumarin, colchicine, platinum, and some miscellaneous structures. The selection of two or more moieties for generating the hybrid drug is generally aided by the observed (or anticipated) synergistic or additive pharmacological activities of each single moiety. This eventually leads to the identification of novel and better active chemical entities with a superior profile as compared to the parent moieties. In addition to the design strategies, this review also highlights the structure–activity relationship (SAR), mechanism of action, and key features of the synthesized anticancer hybrids.
59 citations
References
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TL;DR: The SRB assay provides a sensitive measure of drug-induced cytotoxicity, is useful in quantitating clonogenicity, and is well suited to high-volume, automated drug screening.
Abstract: We have developed a rapid, sensitive, and inexpensive method for measuring the cellular protein content of adherent and suspension cultures in 96-well microtiter plates. The method is suitable for ordinary laboratory purposes and for very large-scale applications, such as the National Cancer Institute's disease-oriented in vitro anticancer-drug discovery screen, which requires the use of several million culture wells per year. Cultures fixed with trichloroacetic acid were stained for 30 minutes with 0.4% (wt/vol) sulforhodamine B (SRB) dissolved in 1% acetic acid. Unbound dye was removed by four washes with 1% acetic acid, and protein-bound dye was extracted with 10 mM unbuffered Tris base [tris (hydroxymethyl)aminomethane] for determination of optical density in a computer-interfaced, 96-well microtiter plate reader. The SRB assay results were linear with the number of cells and with values for cellular protein measured by both the Lowry and Bradford assays at densities ranging from sparse subconfluence to multilayered supraconfluence. The signal-to-noise ratio at 564 nm was approximately 1.5 with 1,000 cells per well. The sensitivity of the SRB assay compared favorably with sensitivities of several fluorescence assays and was superior to those of both the Lowry and Bradford assays and to those of 20 other visible dyes. The SRB assay provides a colorimetric end point that is nondestructive, indefinitely stable, and visible to the naked eye. It provides a sensitive measure of drug-induced cytotoxicity, is useful in quantitating clonogenicity, and is well suited to high-volume, automated drug screening. SRB fluoresces strongly with laser excitation at 488 nm and can be measured quantitatively at the single-cell level by static fluorescence cytometry.
9,019 citations
"Synthesis of some coumarinyl chalco..." refers background or methods in this paper
...Cells were treated with each compound for 48 h, followed by measuring cell growth/proliferation by SRB-based spectrophotometry as described previously [35,36]....
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...The reading of SRB staining is known to accurately reflect the levels of total cellular macromolecules/cell growth/proliferation [36]....
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Journal Article•
TL;DR: Agrawal et al. as mentioned in this paper proposed a method for signal assignment of carbon-13 NMR spectroscopy images of the flavonoid structures and established the aromatic substitution pattern.
Abstract: 1. Introduction (P.K. Agrawal, K.R. Markham). Flavonoid structure variation - nomenclature. Flavonoid structure establishment - general. Revision of flavonoid structures resulting from carbon-13 NMR studies. Carbon-13 NMR spectroscopy - general. 2. Methods for Signal Assignment (P.K. Agrawal). Experimental NMR techniques. Shift and relaxation reagents. Isotopic labelling. Derivatization. 3. Flavonoids (P.K. Agrawal, R.S. Thakur, M.C. Bansal). Flavanones. Flavanonols. Flavones. Flavonols. 3-Methoxyflavones. Flavonoid sulphates. Anthocyanidins. 4. Isoflavonoids (P.K. Agrawal, M.C. Bansal). Isoflavonoids. Coumaronochromones. Pterocarpanoids. Rotenoids. Bi-isoflavanoids. 5. Other Flavonoids (P.K. Agrawal, M.C. Bansal). Neoflavonoids. Auronoids. Homoisoflavonoids and homoflavonoids. Biflavonoids. 6. Flavonoid Glycosides (P.K. Agrawal, M.C. Bansal). Solvent system. Number and identification of the monosaccharides. Interglycosidic linkage. Identification of flavonoid aglycones. Site of glycosylation. Anthocyanins and acylated anthocyanins. 7. Chalconoids (P.K. Agrawal, M.C. Bansal). Chalconoid structure variation - nomenclature. Chalconoids. Chalcanonoids. Chalcanoids. Biflavonoids. Chalconid glycosides. Determination of aromatic substitution pattern. 8. Flavanoids (P.K. Agrawal, M.C. Bansal, L.J. Porter, L. Yeap Foo). Monomeric flavanoids. Condensed proanthocyanidins. Flavanoid esters. Flavanoid-O- and C-glycosides. Miscellaneous flavans. Isoflavanoids. 9. Flavonoid Structure and Carbon-13 NMR Spectroscopy (P.K. Agrawal). C 15 Flavonoids. C 16 Flavonoids. Establishment of the aromatic substitution pattern. (Chapters begin with an Introduction and conclude with References). Abbreviations. Subject Index. Compound Index.
1,049 citations
TL;DR: The thiol reactivity of chalcones is likely to contribute to both cytotoxic and chemoprotective properties of these compounds.
Abstract: Chalcone is a unique template that is associated with several biological activities. In this review, an update of the cytotoxic and chemoprotective activities of chalcones is provided. Cytotoxicity against tumour cell lines may be the result of disruption of the cell cycle, inhibition of angiogenesis, interference with p53-MDM2 interaction, mitochondrial uncoupling or induction of apoptosis. Structural requirements for cytotoxic activity vary according to the mechanisms of action. For anti-mitotic activity, the presence of methoxy substituents, alpha-methylation of the enone moiety and the presence of 2' oxygenated substituents are favourable features. Conformational restraint of the chalcone template generally leads to a decrease in cytotoxic activity. Chemoprotection by chalcones may be a consequence of their antioxidant properties, mediated via inhibition or induction of metabolic enzymes, by an anti-invasive effect or a reduction in nitric oxide production. Hydroxyl and prenyl substituents are associated with antioxidant properties and induction of quinone reductase activities. The thiol reactivity of chalcones is likely to contribute to both cytotoxic and chemoprotective properties of these compounds.
562 citations
Journal Article•
TL;DR: In this article, the authors outline the different bioactivities of a variety of chalcones and describe the cytotoxic, anticancer, chemopreventative and mutagenic properties of a number of CHs followed by an account of various CHs as antimicrobial agents.
Abstract: This review outlines the different bioactivities of a variety of chalcones. The cytotoxic, anticancer, chemopreventative and mutagenic properties of a number of chalcones are described followed by an account of various of these unsaturated ketones as antimicrobial agents. The antiviral, antiprotozoal and insecticidal activities of a variety of chalcones are reviewed as well as the enzyme-inhibitory properties and miscellaneous activities of some of these molecules.
546 citations
TL;DR: Chalcones with 2',3' ',4' '-trimethoxy, 2'',4' -dimethoxy and 4'-hydroxy groups on ring B were synthesized and evaluated in vitro against Plasmodium falciparum (K1) in a [3H] hypoxanthine uptake assay as discussed by the authors.
Abstract: Chalcones with 2‘,3‘,4‘-trimethoxy, 2‘,4‘-dimethoxy, 4‘-methoxy, 4‘-ethoxy, 2‘,4‘-dihydroxy, and 4‘-hydroxy groups on ring B were synthesized and evaluated in vitro against Plasmodium falciparum (K1) in a [3H] hypoxanthine uptake assay. The other ring A was quinoline, pyridine, naphthalene, or phenyl rings with electron-donating or electron-withdrawing substituents of varying lipophilicities. Trimethoxy 6 and 27, dimethoxy 7, 8, 29, and methoxy 31 analogues had good in vitro activities (IC50 < 5 μM). 3-Quinolinyl ring A derivatives were well represented among the active compounds. Hydroxylated chalcones were less active than the corresponding alkoxylated analogues. When evaluated in vivo, 8 and 208 were comparable to chloroquine in extending the lifespan of infected mice. Multivariate data analysis showed that in vitro activity was mainly determined by the properties of ring B. Quantitative structure−activity relationship models with satisfactory predictive ability were obtained for various B ring chalcon...
395 citations
"Synthesis of some coumarinyl chalco..." refers background in this paper
...net activities, including antileishmanial, antiinflammatory, antimitotic, modulation of P-glycoprotein-mediated multidrug resistance, and antimalarial activities, etc [17-22]....
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