In vitro evaluation of newly developed chalcone analogues in human cancer cells

Vincenzo, Rosa De; Ferlini, Cristiano; Distefano, Mariagrazia; Gaggini, C.; Riva, Antonella; Bombardelli, Ezio; Morazzoni, Paolo; Valenti, Piero; Belluti, Federica; Ranelletti, Franco O.; Mancuso, Stefano; Scambia, Giovanni

doi:10.1007/s002800000160

Cited by 87 publications

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“…67 In MDR-positive MCF-7 cells, chalcone analoges were unable to modulate P-glycoprotein function, while quercitin was able to. 68 More recently, quercitin was reported to suppress MDR via a P-gpindependent mechanism. 69 These findings have been supported by a recent study, which show that food and beverages rich in flavonoids increase doxorubicin accumulation in tumor cells.…”

Section: F L a V O N O I D Smentioning

confidence: 99%

Recent advances in the discovery of flavonoids and analogs with high‐affinity binding to P‐glycoprotein responsible for cancer cell multidrug resistance

Boumendjel¹,

Pietro²,

Dumontet³

et al. 2002

Medicinal Research Reviews

158

105

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P-glycoprotein (P-gp) is a plasma membrane glycoprotein that confers multidrug resistance on cells by virtue of its ability to exclude cytotoxic drugs in an ATP-dependent manner. The most commonly considered hypothesis is that P-gp acts as an ATP-driven drug-export pump, the mechanism of which is not understood in detail. Therefore, a tremendous effort is being made to find out modulator molecules to inhibit P-gp. We have been developing flavonoid derivatives as a new class of promising modulators using a new in vitro rational-screening assay based on measurements of the binding-affinity toward the C-terminal nucleotide-binding domain (NBD2) of P-gp. This review is focused on our results obtained with a variety of flavonoids. Structure-activity relationships of flavonoids as potential MDR modulators are reported.

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Section: F L a V O N O I D Smentioning

confidence: 99%

Recent advances in the discovery of flavonoids and analogs with high‐affinity binding to P‐glycoprotein responsible for cancer cell multidrug resistance

Boumendjel¹,

Pietro²,

Dumontet³

et al. 2002

Medicinal Research Reviews

158

105

View full text Add to dashboard Cite

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“…[8][9][10] Thiazolidinones are another class of heterocycle that are reported to possess anti-inflammatory, 11) anti-microbial, 12) anti-proliferative, 13,14) anti-viral, 15) anti-convulsant, 16,17) antifungal, 18) and anti-bacterial properties. 19) Recent reports indicate that these compounds possess anticancer properties.…”

Section: )mentioning

confidence: 99%

Synthesis and Anti-cancer Activity of Novel Thiazolidinone Analogs of 6-Aminoflavone

Moorkoth

2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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Novel heterocyclic analogs were synthesized by combining a flavone nucleus and thiazolidinone ring in an effort to potentiate the existing anti-cancer activity of flavone. The syntheses of 6-aminoflavone, 6-amino-3-methoxyflavone, 6-amino-3-methoxy-3′,4′-dimethxyflavone and their corresponding thiazolidinone analogs were performed. Fifteen novel analogs were synthesized and evaluated for their anti-cancer activity using cell-based assay techniques and in vivo testing. As expected, the analogs improved cytotoxicity and were shown to increase the life span of cancer-bearing mice. Cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays in HeLa, MDA-MB-435, and Vero cell lines. In vivo evaluation of anti-cancer activity performed in albino mice bearing Dalton's ascites carcinoma showed that the new analogs enhanced life span and prevented increases in body weight owing to tumor volumes. Moreover, cell-cycle analysis and Hoechst staining analysis proved the apoptotic potential of these analogs. Preliminary pharmacokinetic evaluation was carried out on the synthesized compounds to determine the lipophilicity and pK a . Lipophilicity was determined using high-performance liquid chromatography and the results showed a direct correlation between the observed anti-cancer activity and log P value, while pK a values indicated the ionizing range which is a prediction tool for solubility and permeability.Key words aminoflavone; thiazolidinone; anticancer; cytotoxicity; lipophilicity; in vivo activity Polyphenols such as flavonoids that contain chromone pharmacophore are known for their wide range of pharmacological activities. It is important to note that these compounds are non-toxic at concentrations that are normally consumed in a normal diet. A flavonoid-rich diet is also considered as a prophylactic treatment for cancer. Various clinical studies performed on flavonoids indicate that these molecules are potent chemotherapeutic agents against cancer. The anticancer activity of flavonoids is mainly by the inactivation of carcinogens, cell-cycle arrest, and by the induction of apoptosis.1) The approach to anticancer drug discovery is to develop cytotoxic agents that can differentiate cancer cells and normal cells. One way of synthesizing molecules with lesser toxicity would be to adopt the molecularly targeted therapeutics, which will provide sufficient selectivity to a receptor.2) The role of flavonoids in chemoprevention of cancer is well established. 3)Major highlight of flavonoids is that they act through multiple mechanisms such as angiogenesis inhibition, inactivation of carcinogen, 4-7) arresting the cell cycle and apoptosis induction. [8][9][10] Thiazolidinones are another class of heterocycle that are reported to possess anti-inflammatory, 11) anti-microbial, 12) anti-proliferative, 13,14) anti-viral, 15) anti-convulsant, 16,17) antifungal, 18) and anti-bacterial properties. 19) Recent reports indicate that these compounds possess anticancer properties. 20)Aminofla...

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“…Авторы статьи [16] показали, что осно-вания Манниха, полученные из халконов, проявляют цитотоксичность против линий Р338 и L1210 клеток лейкемии мышей, а также некоторых линий раковых клеток человека. Основания Манниха халконов с гетероциклическим фрагментом исследо-ваны на цитотоксическую активность в от-ношении четырех линий раковых клеток человека (РС-3, MCF-7, KB, KB-VIN), при этом производные с морфолиновым заме-стителем при С3 или С5 и с пиридиновым или фенильным ядрами при С2 проявляют высокую цитотоксическую активность.…”

Section: основная частьunclassified

Dependence of Biological Activity of Chalcones on Their Structure

Степкина¹,

Великородов²

2015

ФИ (FR)

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Обзор посвящен рассмотрению зависимости биологической активности 1,3-дифенил-2-пропен-1-онов (халконов) от строения молекул. Выявлены фармакофорные группы, обуславливающие проявление анти-микробной, противогрибковой, противоопухолевой, антиоксидантной, цитотоксической, антипролифера-тивной, противовоспалительной, гипергликемической, гепатопротекторной и других видов активности. На-личие хлорхинолинового фрагмента обеспечивает проявление антималярийной и антиамебной активности. Халконы с электронодонорными заместителями (метокси-, гидрокси-и др. группами), а также содержащие один -два атома хлора или фтора показывают наибольшую противомикробную и противогрибковую актив-ность. Основания Шиффа, полученные на основе халконов с гетероциклическим фрагментом, а также бор-содержащие халконы характеризуются высокой цитотоксичностью в отношении раковых клеток человека линий РС-3, MCF-7, KB, KB-VIN. 1,3-Дифенил-2-пропен-1-оны с оксатиолоновым циклом помимо цито-токсичности проявляют активность в отношении Micobacterium tuberculosis H 37 Rv. Халконы, содержащие в бензольном кольце ацетамидную группу в положении 4, проявляют значительную антиноцицептивную ак-тивность. Дигидроксопроизводные халконов с орто-и пара-расположением ОН групп проявляют высокую антиоксидантную активность. Положение двух гидроксильных групп в бензольном кольце В халкона яв-ляется важным структурным фактором их антирадикальной активности. Вицинально диоксигенированные халконы, а также халконы с цепью пропаноламина в пара-положении показывают высокую антигиперглике-мическую активность, хлорсодержащие халконы -антипротозойную активность, а халконы с триазольным, пиррольным и бензотриазольным кольцами -антипаразитарную активность. Присутствие 1,4-диоксанового цикла в структуре приводит к появлению антигепатотоксической активности, которая усиливается наличием в положении 2 диоксанового цикла 2-гидроксиметильной группы.Ключевые слова: халконы, биологическая активность, цитотоксичность, противоопухолевая, антиоксидантная, противомикробная, противовоспалительная, антидиабетическая активность DEPENDENCE OF BIOLOGICAL ACTIVITY OF CHALCONES ON THEIR STRUCTUREStepkina N.N., Velikorodov A.V. Astrakhan State University, Astrakhan, e-mail: org@asu.edu.ruThis review is devoted to the analysis of 1,3-diphenyl-2-propene-1-ones (chalcones) biological activity dependence on their molecular structure. Pharmacophores which determine antimicrobial, antifungal, antibacterial, anticancer, antioxidant, cytotoxic, antiproliferative, anti-infl ammatory, hyperglycemic, hepatoprotective and other activities were found out. The presence of chloroquinolinic fragment provides antimalarial and antiamebic activities. Chalcones which have electron donating substituents (methoxy-, hydroxy-and others) or 1-2 chlorine or fl uorine atoms show maximum antimicrobial and antifungal activity. Schiff's bases obtained from chalcones with heterocyclic fragment as well as boron-containing chalcones are characterized with high cytotoxic activity against human cancer cell lines РС-3, MCF-7, KB, KB-V...

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In vitro evaluation of newly developed chalcone analogues in human cancer cells

Abstract: Newly developed S1 and S2 chalcones have a different but higher antitumor activity than quercetin and could be considered as potential new anticancer drugs.

Cited by 87 publications

References 0 publications

Recent advances in the discovery of flavonoids and analogs with high‐affinity binding to P‐glycoprotein responsible for cancer cell multidrug resistance

Recent advances in the discovery of flavonoids and analogs with high‐affinity binding to P‐glycoprotein responsible for cancer cell multidrug resistance

Synthesis and Anti-cancer Activity of Novel Thiazolidinone Analogs of 6-Aminoflavone

Dependence of Biological Activity of Chalcones on Their Structure

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