Antiproliferative activities of some 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenone derivatives against 60 human cancer cell lines

234 derivatives of 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenones were synthesized and tested for antitumor activity in vitro against human cancer cell lines in NCI (National Cancer Institute, USA) bioassay. It was shown high cytostatic and cytotoxic activity for the tested compounds 1-8 (GI...

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Опубліковано в: :Біополімери і клітина
Дата:2004
Автори: Prykhod'ko, A.O., Dubinina, G.G., Khilya, V.P., Yarmoluk, S.M.
Формат: Стаття
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Опубліковано: Інститут молекулярної біології і генетики НАН України 2004
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Цитувати:Antiproliferative activities of some 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenone derivatives against 60 human cancer cell lines / A.O. Prykhod'ko, G.G. Dubinina, V.P. Khilya, S.M. Yarmoluk// Біополімери і клітина. — 2004. — Т. 20, № 1-2. — С. 159-163. — Бібліогр.: 24 назв. — англ.

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Digital Library of Periodicals of National Academy of Sciences of Ukraine
id nasplib_isofts_kiev_ua-123456789-157205
record_format dspace
spelling Prykhod'ko, A.O.
Dubinina, G.G.
Khilya, V.P.
Yarmoluk, S.M.
2019-06-19T17:56:32Z
2019-06-19T17:56:32Z
2004
Antiproliferative activities of some 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenone derivatives against 60 human cancer cell lines / A.O. Prykhod'ko, G.G. Dubinina, V.P. Khilya, S.M. Yarmoluk// Біополімери і клітина. — 2004. — Т. 20, № 1-2. — С. 159-163. — Бібліогр.: 24 назв. — англ.
0233-7657
DOI:http://dx.doi.org/10.7124/bc.0006A3
https://nasplib.isofts.kiev.ua/handle/123456789/157205
547.745:576.385.5
234 derivatives of 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenones were synthesized and tested for antitumor activity in vitro against human cancer cell lines in NCI (National Cancer Institute, USA) bioassay. It was shown high cytostatic and cytotoxic activity for the tested compounds 1-8 (GI50 3.44-41.1 mM and LC50 from 49.6 mM). The relationship between structures of the tested compounds and their antiproliferative activities is discussed.
Синтезовано 234 похідних 7-гідрокси-3-арилокси-2-трифторметил-4Н-4-хроменону та досліджено їхню протиракову ак­тивність на лініях ракових клітин людини у Національному Інституті Раку (США). Сполуки 1–8 виявили високу цитостатичну та цитотоксичну активність (GI50 3,44–41,1 мкМ та LC50 від 49,6 мкМ). Обговорюється взаємозв'язок між структурою тестованих сполук та їхньою проліферативною активністю.
Синтезированы 234 производных 7-гидрокси-З-арилокси-2-mpu-фторметил-4Н-4-хроменона и исследована их противораковая активность на линиях раковых клеток человека в Националь­ном Институте Рака (США). Соединения 1—8 проявили высокую цитостатическую и цитотоксическую активность (Gl50 3,44—41,1 мкМ и LC50 от 49,6 мкМ). Обсуждается взаимосвязь между структурой тестированных соединений и их пролиферативной активностью.
We are grateful to the Na­tional Cancer Institute of the USA for generous support of our programs.
uk
Інститут молекулярної біології і генетики НАН України
Біополімери і клітина
Ювілеї
Antiproliferative activities of some 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenone derivatives against 60 human cancer cell lines
Антипроліферативна активність деяких похідних 7-гідрокси-З- арилокси-2-трифторметил-4Н-4-хроменону проти 60 ліній клітин раку людини
Антипролиферативная активность некоторых производных 7- гидрокси-3-арилокси-2-трифторметил-4Н-4-хроменона против 60 линий раковых клеток человека
Article
published earlier
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
title Antiproliferative activities of some 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenone derivatives against 60 human cancer cell lines
spellingShingle Antiproliferative activities of some 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenone derivatives against 60 human cancer cell lines
Prykhod'ko, A.O.
Dubinina, G.G.
Khilya, V.P.
Yarmoluk, S.M.
Ювілеї
title_short Antiproliferative activities of some 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenone derivatives against 60 human cancer cell lines
title_full Antiproliferative activities of some 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenone derivatives against 60 human cancer cell lines
title_fullStr Antiproliferative activities of some 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenone derivatives against 60 human cancer cell lines
title_full_unstemmed Antiproliferative activities of some 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenone derivatives against 60 human cancer cell lines
title_sort antiproliferative activities of some 7-hydroxy-3-aryloxy-2-trifluoromethyl-4h-4-chromenone derivatives against 60 human cancer cell lines
author Prykhod'ko, A.O.
Dubinina, G.G.
Khilya, V.P.
Yarmoluk, S.M.
author_facet Prykhod'ko, A.O.
Dubinina, G.G.
Khilya, V.P.
Yarmoluk, S.M.
topic Ювілеї
topic_facet Ювілеї
publishDate 2004
language Ukrainian
container_title Біополімери і клітина
publisher Інститут молекулярної біології і генетики НАН України
format Article
title_alt Антипроліферативна активність деяких похідних 7-гідрокси-З- арилокси-2-трифторметил-4Н-4-хроменону проти 60 ліній клітин раку людини
Антипролиферативная активность некоторых производных 7- гидрокси-3-арилокси-2-трифторметил-4Н-4-хроменона против 60 линий раковых клеток человека
description 234 derivatives of 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenones were synthesized and tested for antitumor activity in vitro against human cancer cell lines in NCI (National Cancer Institute, USA) bioassay. It was shown high cytostatic and cytotoxic activity for the tested compounds 1-8 (GI50 3.44-41.1 mM and LC50 from 49.6 mM). The relationship between structures of the tested compounds and their antiproliferative activities is discussed. Синтезовано 234 похідних 7-гідрокси-3-арилокси-2-трифторметил-4Н-4-хроменону та досліджено їхню протиракову ак­тивність на лініях ракових клітин людини у Національному Інституті Раку (США). Сполуки 1–8 виявили високу цитостатичну та цитотоксичну активність (GI50 3,44–41,1 мкМ та LC50 від 49,6 мкМ). Обговорюється взаємозв'язок між структурою тестованих сполук та їхньою проліферативною активністю. Синтезированы 234 производных 7-гидрокси-З-арилокси-2-mpu-фторметил-4Н-4-хроменона и исследована их противораковая активность на линиях раковых клеток человека в Националь­ном Институте Рака (США). Соединения 1—8 проявили высокую цитостатическую и цитотоксическую активность (Gl50 3,44—41,1 мкМ и LC50 от 49,6 мкМ). Обсуждается взаимосвязь между структурой тестированных соединений и их пролиферативной активностью.
issn 0233-7657
url https://nasplib.isofts.kiev.ua/handle/123456789/157205
citation_txt Antiproliferative activities of some 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenone derivatives against 60 human cancer cell lines / A.O. Prykhod'ko, G.G. Dubinina, V.P. Khilya, S.M. Yarmoluk// Біополімери і клітина. — 2004. — Т. 20, № 1-2. — С. 159-163. — Бібліогр.: 24 назв. — англ.
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fulltext ISSN 0233-7657. Біополімери і клітина. 2004. Т. 20. № 1-2 Antiproliferative activities of some 7-hydroxy-3- aryloxy-2-trifluoromethyl-4H-4-chromenone derivatives against 60 human cancer cell lines A. O. Prykhod'ko, G. G. Dubinina, V. P. Khilya1, S. M. Yarmoluk Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine 150 Acad. Zabolotnoho str., Kyiv, 03143, Ukraine Kyiv National Taras Shevchenko University 64 Volodymyrska str., Kyiv, 01033, Ukraine 234 derivatives of 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenones were synthesized and tested for antitumor activity in vitro against human cancer cell lines in NCI (National Cancer Institute, LISA) bioassay. It was shown high cytostatic and cytotoxic activity for the tested compounds I—8 (GIso 3.44—41.1 fiM and LCso from 49.6 цМ). The relationship between structures of the tested compounds and their antiproliferative activities is discussed. Introduction. Isoflavonoids are a large group of na­ turally occuring phenolic compounds ubiquitously dis­ tributed in the plant kingdom. The biological activity of isoflavonoids is related to their antioxidative effects [1—3] and influences tumor cell proliferation, dif­ ferentiation and apoptosis [4—8 ]. Antiproliferative activities of isoflavonoids include inhibition of protein tyrosine kinase [9—12], DNA topoisomerase I and II [13, 14], protein kinase С and phosphoinositol kinase [15—17], casein kinase II [18]. Inhibition of cyclin- dependent kinases has been also described [19]. The synthetic flavonoid flavopiridol (phase I clinical and pharmacokinetic trial) has been shown to be a potent inhibitor of cdc2 kinase activity (fig. 1) [20, 21 ]. During last years we were interested in the synthesis of isoflavonoids aimed at finding compounds with biological activity [22, 23]. The present paper deals with the synthesis of a combinatorial series of 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chro- menone derivatives as potential antitumor agents. Materials and Methods. Chemical synthesis of the library of 234 chromenone derivatives was per- © A. O. P R Y K H O D ' K O , G. G. DUBININA, V. P. KHILYA, S. M. YARMOLUK, 2 0 0 4 formed by modification of the methods reported before [22—24]. Structure and purity of synthesized compounds were confirmed by 'H NMR spectroscopy. The spectra were obtained with Varian VXR-300 NMR spectrometer at 300 MHz. The synthesized compounds were tested for cyto­ toxic and antitumor activity in vitro in collaboration with National Cancer Institute of the U.S.A. (http://dtp.nci.nih.gov/index.html). The calculated measurement of effect was Percentage Growth (PG). The effect of the compound on a cell line was calculated according to the following two expressions: If (Mean OD t e s l - Mean OD l z e r o) > 0, then PG - 100- (Mean OD t e s t - Mean O D ^ / M e a n OD c l r ,-Mean СЮ1гего); If (Mean OD l e s t - Mean OD l z e r o) < 0, then PG = 100- (Mean OD t e s, - Mean OD t z e r o)/Mean where Mean OD t z e r o , Mean OD l e s l and Mean ODctr, are the averages of optical density measurements of SRB-derived color just before cells exposure to the tested compounds, after 48 hours of exposure, and after 48 hours without any exposure of cells to the 159 http://dtp.nci.nih.gov/index.html PRYKHOD'KO А. О. ET AL. ОН о Fig. 1. Structure of flavopiridol (FLAP or NSC 649890) stage the pre-screening of all 234 compounds was carried out against 3 human cancer cell lines, MCF7 (Breast cancer), NCI-H460 (Non-small cancer cell lung) and SF-268 (CNS), at 10"4 M concentration. Compounds 1—8 (fig. 2) demonstrated antiproli­ ferative activity (PG < 32 %) and were selected for the advanced testing against 60 human cancer cell lines at five different concentrations (10 - 8—10 4 M). Experimental data for compounds 1—8 in repre­ sentative cell lines are shown in tables 1, 2. Tested compounds 1—8 were found to inhibit proliferation of tumor cells in the range of GI 5 0 3.44—41.1 /иМ, and exhibited cytotoxic activity against cancer cell lines (LC 5 0 from 49.6 fiM). A number of cell lines including RPMI-8226 Leukemia, SK-MEL-5 Melanoma, T-47D Breast cancer and HCT-116 Colon cancer showed significant sensitivity to these compounds. 234 tested compounds containes various sub- stituents at C-3, C-7 and C-8 positions. Active Fig. 2. Structures of cytotoxic antitumor 7-hydroxy-3-aryl- oxy-2-trifluoromethyl-4H-4- chromenone derivatives 1—8 selected after pre-screening tested compounds, respectively. The response para- compounds 2-8 containes bulky hydrophobic sub- meters GI 5 0, TGI, LC 5 0 are interpolated values repre- stituent (2'-naphthyloxy or 4'-phenylphenoxy) at C-3 senting the concentrations at which PG is +50,0 and position and hydrophilic substituents, dialkylami- -50, respectively. nomethyl at C-8 or O-acyl at C-7 positions. The Results and Discussion. The combinatorial lib- presence of phenyl residue at C-3 position either rary of 234 derivatives of 7-hydroxy-3-aryloxy-2- substituted or non-substituted, resulted in the loss of trifluoromethyl-4H-4-chromenone was synthesized antiproliferative activity. The presence of chlorine and tested for antitumor activity in vitro against a t o m a t t h e orffto-position in structure 1 is critical for human cancer cell lines in NCI bioassay. At the first t h e biological activity, as meta- or para-substitution 160 ACTIVITIES OF C H R O M E N O N E D E R I V A T I V E S AGAINST CANCER CELL Table I Antiproliferative activities (GI50 and TGI) of 7-hydroxy-3-aryloxy-2-trifluoromethyl-4H-4-chromenone derivatives 1—8 against selected human cancer cell lines *ND — not determined. leads to significant decrease of antiproliferative acti­ vity. At the same time, the activity of 2',4'-dichloro derivative was only slightly lower. Introduction of some alkylaminomethyl groups into C-8 position of structure 1 also resulted in the activity decrease. Activities of compounds 2, containing trifluoromethyl group, and 3 were close. Analogs of structure 1, compounds 4—8 without CF3-group at C-2 position showed decreased activities. Substitution of 2-naph- thyloxy moiety at C-3 position of compounds 4—8 for 4'-phenylphenoxy group decreased the activity. Com­ pound 8 demonstrated significant inhibition of many 161 P R Y K H O D ' K O А. О. E T AL. Table 2 Cytotoxic activity of 7-hydroxy-3-phenoxy-2-trifluoromethyl-4H-4-chromenone derivatives 1—8 toward selected human cancer cell lines *ND — not determined. cell lines. Further studies will be performed on the optimization of the active structures 1—8 found in the present data set. Supporting Information Available: Pre-screening data for 234 tested compounds and ! H NMR spectra for compounds 1—8. This material is available free of charge via the Internet at www.yarmoluk.org.ua. Acknowledgement. We are grateful to the Na­ tional Cancer Institute of the USA for generous support of our programs. А. О. Приходько, Г. Г. Дубініна, В. П. Хиля, С. М. Ярмолюк Антипроліферативна активність деяких похідних 7-гідрокси-З- арилокси-2-трифторметил-4Н-4-хроменону проти 60 ліній клітин раку людини Резюме Синтезовано 234 похідних 7-гідрокси-3-арилокси-2-трифтор- метил-4Н-4-хроменону та досліджено їхню протиракову ак­ тивність на лініях ракових клітин людини у Національному Інституті Раку (США). Сполуки 1—4? виявили високу цито- статичну та цитотоксичну активність (GISQ 3,44—41,1 мкМ та LCS0 від 49,6 мкМ). Обговорюється взаємозв'язок між структурою тестованих сполук та їхньою проліферативною активністю. А. А. Приходько, Г. Г. Дубинина, В. П. Хиля, С. Н. Ярмолюк Антипролиферативная активность некоторых производных 7- гидрокси-3-арилокси-2-трифторметил-4Н-4-хроменона против 60 линий раковых клеток человека Резюме Синтезированы 234 производных 7-гидрокси-З-арилокси-2-mpu- фторметил-4Н-4-хроменона и исследована их противораковая активность на линиях раковых клеток человека в Националь­ ном Институте Рака (США). Соединения 1—8 проявили высокую цитостатическую и цитотоксическую активность (Glso 3,44—41,1 мкМ и LC50 от 49,6 мкМ). Обсуждается взаимосвязь между структурой тестированных соединений и их пролиферативной активностью. REFERENCES 1. Cotelle N. Role of flavonoids in oxidative stress / / Curr. Top. Med. Chem.—2001.—1.—P. 569—590. 2. Van Acker F. A. A., Hageman J. A., Haenen G. R. M. M., Van der Vijgh W. J. F., Bast A., Menge W. M. P. B. Synthesis of novel 3,7-substituted-2-(3',4'-dihydroxyphenyl)flavones with improved antioxidant activity III. Med. Chem.—2000.— 43.—P. 3752—3760. 3. Owen R. W., Giacosa A., Hull W. E., Haubner R., Spiegel- holder В., Bartsch H. The antioxidant/anticancer potential of phenolic compounds isolated from olive oil / / Eur. J. Can­ cer.—2000.—36.—P. 1235—1247. 4. Jing Y., Waxman S. Structural requirements for differentia­ tion-induction and growth-inhibition of mouse erythroleukemia cells by isoflavones / / Anticancer Res. —1995.—15.— P. 1147—1152. 5. 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