Rational design, synthesis and structure–activity relationships of antitumor (E)-2-benzylidene-1-tetralones and (E)-2-benzylidene-1-indanones

Shih, Hsiencheng; Deng, Lynn; Carrera, Carlos J.; Adachi, Souichi; Cottam, Howard B.; Carson, Dennis A.

doi:10.1016/s0960-894x(00)00032-9

Cited by 38 publications

(26 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several representatives of these classes of compounds showed remarkable antiproliferative and cytotoxic effect-in a cytotoxicity screening against A431 human adenocarcinoma cells. Additional biological effects have been reported also and described previously elsewhere [12][13][14][15].…”

Section: Introductionmentioning

confidence: 63%

Lipophilicity and antiproliferative activity profiling of 2-benzylidencycloalkanones

Hallgas

Dobos

Agócs

et al. 2007

Journal of Chromatography B

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 63%

Lipophilicity and antiproliferative activity profiling of 2-benzylidencycloalkanones

Hallgas

Dobos

Agócs

et al. 2007

Journal of Chromatography B

View full text Add to dashboard Cite

“…Furthermore, based on the assigned structure, the other nitrogen atom resonates at δ = 299.7 ppm and correlates with the N-attached aromatic protons; however, its signal is not intense (the 1 H- 15 …”

Section: First Synthetic Partmentioning

confidence: 99%

“…In this context, the initial design of the target compounds was based on reports establishing that ring systems containing the (E)-2-benzylidene-1-tetralones and (E)-2-benzylidene-1-tetralone backbone exhibit remarkable cytotoxic activity [15], initiating the use of α-tetralones as precursors for the synthesis of bioactive compounds [16,17]. In another application, 6-methoxytetralone has been utilized as a substrate for the construction of steroids [18].…”

Section: Introductionmentioning

confidence: 99%

Novel conformationally constrained pyrazole derivatives as potential anti-cancer agents

Kasiotis

Tzanetou

Stagos

et al. 2015

Zeitschrift Für Naturforschung B

View full text Add to dashboard Cite

The synthesis of 17 novel conformationally constrained pyrazole derivatives is reported herein, along with the assessment of their anti-proliferative and antiangiogenic activities. The evaluation of their inhibitory effect on cell proliferation against HepG2, HeLa, and MCF-7 cells revealed the pyrrolo[2,3-g]indazole 23 as a potent inhibitor of cell growth with IC 50 values of 5 μm. Additionally, the inhibition of vascular endothelial growth factor by pyrazoles 20 and 23 (30 % and 35 %, respectively) in HeLa supernatant cells was evidenced. These findings highlight the usefulness of these compounds as potential scaffolds for the design and development of novel anticancer agents with pronounced anti-angiogenic activity.

show abstract

“…For comparison, we also prepared a chalcone ( 3 ) where the indole was replaced by a trimethoxyphenyl group, a key structural feature that occurred in a number of synthetic and natural products with anticancer activities, including combretastantin A4 and colchicine. 31–35 Similar compounds were known to induce cell cycle arrest and apoptosis of cancer cells. 36 …”

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

View full text Add to dashboard Cite

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...

show abstract

Rational design, synthesis and structure–activity relationships of antitumor (E)-2-benzylidene-1-tetralones and (E)-2-benzylidene-1-indanones

Cited by 38 publications

References 11 publications

Lipophilicity and antiproliferative activity profiling of 2-benzylidencycloalkanones

Lipophilicity and antiproliferative activity profiling of 2-benzylidencycloalkanones

Novel conformationally constrained pyrazole derivatives as potential anti-cancer agents

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

Contact Info

Product

Resources

About