Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

Jandial, Danielle; Blair, Christopher; Zhang, Sai‐Yang; Krill, Lauren; Zhang, Yanbing; Zi, Xiaolin

doi:10.2174/1568009614666140122160515

Cited by 112 publications

(87 citation statements)

References 128 publications

(142 reference statements)

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“…Most of the articles report about the potential of the investigated chalcones to induce apoptosis, induce mitochondrial uncoupling, inhibit transcription factors and show antimitotic properties. There are several ongoing projects to find more effective synthetic chalcone analogues based on the above known mechanisms of natural chalcones (Ni et al 2004;Go et al 2005;Batovska and Todorova 2010;Jandial et al 2014).…”

Section: Antiprotozoal Propertiesmentioning

confidence: 99%

“…Further details, including antitumor effects of synthetic chalcones, are discussed in reviews on this particular field (Dimmock et al 1999;Go et al 2005;Batovska and Parushev 2010;Zhang et al 2013a;Jandial et al 2014). …”

Section: Antiprotozoal Propertiesmentioning

confidence: 99%

“…Each review summarized the latest developments on flavonoid research mostly concentrating on structure and occurrence of natural flavonoids. Biological activities of natural and synthetic chalcones have been reviewed in several recent publications (Dimmock et al 1999;Ni et al 2004;Go et al 2005;Nowakowska 2007;Batovska and Parushev 2010;Batovska and Todorova 2010;Gupta et al 2010;Orlikova et al 2011;Rahman 2011;Sahu et al 2012;Kumar et al 2013;Zhang et al 2013a;Jandial et al 2014). Most of these reviews deal with natural and synthetic chalcones from a particular (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Naturally occurring chalcones and their biological activities

2014

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The aim of this review is to summarize the various naturally occurring chalcone compounds which have been isolated from different plants. Chalcones considered as obligate intermediated in flavonoid biosynthesis but they do not accumulate to appreciable degree in most plants. The largest number of natural chalcones has been isolated from species of the Leguminosae, Asteraceae and Moraceae families. Chalcone accumulating plants have often been used in traditional medicine and chalcones have therefore been studied and reported to possess many beneficial biological effects including anti-inflammatory, antimicrobial, antifungal, antioxidant, cytotoxic, antitumor and chemopreventive activities. Previously published reviews on this topic survey the biological activities of natural and synthetic chalcones but there are no comprehensive contributions on occurrence and biological activities of natural chalcones. The present study provides an overview of hydroxy or/and methoxy-substituted chalcones, methylated, prenylated, geranylated and other monomeric derivatives, chromeno-and furanochalcones, dimeric chalcones and dihydrochalcone derivatives focusing on their biosynthesis, natural sources and biological activities. On the basis of 608 references, this review covers the phytochemistry and biological activity of natural chalcones, describing 646 compounds have been appeared in the literature since 1975. The summary is aimed to initiate further pharmacobotanical, biotechnological and medicinal studies on the field of chalcone research.

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Section: Antiprotozoal Propertiesmentioning

confidence: 99%

Section: Antiprotozoal Propertiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Naturally occurring chalcones and their biological activities

2014

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“…They are absorbed through daily diet and show promising cancer chemopreventive role [14]. Cytotoxic and anticancer activities are mediated by modulating important molecular pathways or targets including, P-glycoprotein-mediated multidrug resistance, m-TOR pathway, β-catenin degradation, STAT3, tumour vasculature, cell death induction, tubulin polymerization inhibition, NF-kappa B pathway, androgen and estrogen receptor signalling, p53 pathway etc., [15]. Aforementioned properties motivated us to synthesize and evaluate chalcones as potential cytotoxic agents.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Characterization and Computational Evaluation of Novel Isobutychalcones as Cytotoxic Agents: Part-A

Shahanaaz³

2016

Preprint

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A series of novel isobutylchalcones (A1-A20) were prepared, evaluated for their cytotoxic activity and characterized by FTIR, 1 H NMR, 13 C NMR, and elemental analysis data. The logic behind the design is to synthesize and compare chalcones containing electron releasing lipophilic isobutyl substituent on aromatic ring A and the B ring with aromatic ring containing a range of electron releasing and electron withdrawing groups as well as heteroaromatic rings for their cytotoxic activity. The compounds were tested against HT-29 (colon cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer) cell lines using methotrexate (IC50 12 ± 1 (HT-29), 9 ±1 (MCF-7) 5 ± 1 (DU-145)) as reference standard. Compound A6 having 2,4-difluorphenyl moiety was most potent of the series against all the three cell lines and notably A6 was mainly effective against DU-145 cell lines with an IC50 value of 18 µg/mL. The critical structural features required for the activity against all the cell lines were identified through pharmacophore model using PHASE TM which has recognised a 5 point AHHRR model and is consistent with the cytotoxic activity of the tested compounds.

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“…All the new compounds were characterized by 1 H NMR and MS spectra and their purity is >90% by reverse phase HPLC analyses. 36 In most cases, the products precipitated from the react solution and were isolated by filtration and washing with cold water and ethanol. Typically the isolated yields ranged from 60% to 90%.…”

mentioning

confidence: 99%

Novel synthetic chalcones induce apoptosis in the A549 non-small cell lung cancer cells harboring a KRAS mutation

Hedblom

Koerner

et al. 2016

Bioorganic & Medicinal Chemistry Letters

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A series of novel chalcones were synthesized by the Claisen-Schmidt condensation reaction of tetralones and 5-/6-indolecarboxaldehydes. Treatment of human lung cancer cell line harboring Kras mutation (A549) with the chalcones induced dose-dependent apoptosis. Cell cycle analyses and Western blotting suggested the critical role of the chalcones in interrupting G2/M transition of cell cycle. SAR study demonstrated that substituent on the indole N atom significantly affects the anticancer activity of the chalcones, with methyl and ethyl providing the more active compounds (EC 50 : 110-200 nM), Compound 1g was found to be >4-fold more active in the A549 cells (EC 50 : 110 nM) than in prostate (PC3) or pancreatic cancer (CLR2119, PAN02) cells. Furthermore, compound 1l selectively induced apoptosis of lung cancer cells A549 (EC 50 : 0.55 μM) but did not show measurable toxicity in the normal lung bronchial epithelial cells (hBEC) at doses as high as 10 μM, indicating specificity towards cancer cells. Graphical Abstract KeywordsChalcone; Cell cycle; Apoptosis; KRAS; Non-small cell lung cancer * Corresponding authors: LS: Tel.: +1-617-667-1902; lsun1@bidmc.harvard.edu. Or BW: Tel: 617-735-2846; bwegiel@bidmc.harvard.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Chalcone is a key structural moiety occurring in a number of natural products known to have broad biological activities, including curcumin 3 and xanthohumol. [4][5] It has gained considerable interests in the synthesis of novel anticancer agents with diverse of mechanisms of action. 6-14 HHS Public AccessWe had previously described indole and indazoline series of anticancer agents capable of overcoming multi-drug resistance [15][16][17][18] . Herein we report the identification and preliminary structure-activity relationship (SAR) findings of novel indolyl-tetralone chalcones in the A549 NSCLC cell line, a widely used in vitro model system for investigating KRAS mutation. Our survey of published literature indicated that there were no known chalcones that contain the same key moieties of tetralone and 5-/6-indolyl group. [19][20][21][22][23][24][25][26][27][28] We report that a number of the novel chalcones were highly potent in inducing apoptosis of A549 cells, with sub-μM EC 50 , which are not commonly observed in reported synthetic chalcones. Among them, compound 1l demonstrated preferential cytotoxicity in A549 cells (EC 50 : 0.55 μM) and did not show any toxicity in the normal lung epithelial cells at concentrations ranging from 0.01 to 10 μM.The indolyl-tetralone chalcones (1 and 2) were synthesized...

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Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

Cited by 112 publications

References 128 publications

Naturally occurring chalcones and their biological activities

Naturally occurring chalcones and their biological activities

Design, Synthesis, Characterization and Computational Evaluation of Novel Isobutychalcones as Cytotoxic Agents: Part-A

Novel synthetic chalcones induce apoptosis in the A549 non-small cell lung cancer cells harboring a KRAS mutation

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