Synthesis of aminoanthraquinone derivatives and their in vitro evaluation as potential anti-cancer drugs

Katzhendler, Jehoshua; Gean, K.F.; Bar-Ad, Gidon; Tashma, Zeev; Ben-Shoshan, Raphael; Ringel, Israel; Bachrach, Uriel; Ramu, A

doi:10.1016/0223-5234(89)90159-1

Cited by 26 publications

(7 citation statements)

References 36 publications

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“…All commercial reagent grade chemicals were used without further purification. Polyamides 1a-c [31], aminoalkyl anthraquinones 2 [32] and 3 [33], and [PtCl(en)(NCEt)]Cl 6 [8] were prepared according to reported procedures and details are provided in the Supporting Information along with NMR spectra. The spectroscopic data were consistent with data reported in the literature.…”

Section: Methodsmentioning

confidence: 99%

Novel polyamide amidine anthraquinone platinum(II) complexes: cytotoxicity, cellular accumulation, and fluorescence distributions in 2D and 3D cell culture models

Bryce

Klein

et al. 2021

J Biol Inorg Chem

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1-and 1,5-Aminoalkylamine substituted anthraquinones (AAQs, 1C3 and 1,5C3) were peptide coupled to 1-, 2-, and 3-pyrrole lexitropsins to generate compounds that incorporated both DNA minor groove and intercalating moieties. The corresponding platinum(II) amidine complexes were synthesized through a synthetically facile amine-to-platinum mediated nitrile 'Click' reaction. The precursors as well as the corresponding platinum(II) complexes were biologically evaluated in 2D monolayer cells and 3D tumour cell models. Despite having cellular accumulation levels that were up to five-fold lower than that of cisplatin, the platinum complexes had cytotoxicities that were only three-fold lower. Accumulation was lowest for the complexes with two or three pyrrole groups, but the latter was the most active of the complexes exceeding the activity of cisplatin in the MDA-MB-231 cell line. All compounds showed moderate to good penetration into spheroids of DLD-1 cells with the distributions being consistent with active uptake of the pyrrole containing complexes in regions of the spheroids starved of nutrients.

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Section: Methodsmentioning

confidence: 99%

Novel polyamide amidine anthraquinone platinum(II) complexes: cytotoxicity, cellular accumulation, and fluorescence distributions in 2D and 3D cell culture models

Bryce

Klein

et al. 2021

J Biol Inorg Chem

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“…All the obtained results suggested that the substituent at the nitrogen of 4-(aminopropargyl)-1-hydroxyanthraquinones increased the cytotoxicity. There have been previous studies on the anticancer properties of aminoanthraquinones with the aminoalkylamino side chains at the 1-1,4 − 1,5-or 1,8-positions [41][42][43][44][45]. These reports suggest that the substitution by 1-(N,N-dimethylamino)ethylamine side chain led to optimal activity: compounds with 1-(N,N-dimethylamino)propylamine substituent shown two fold decrease of cytotoxicity on cancer cell lines [44].…”

Section: Chemical Synthesismentioning

confidence: 97%

“…These reports suggest that the substitution by 1-(N,N-dimethylamino)ethylamine side chain led to optimal activity: compounds with 1-(N,N-dimethylamino)propylamine substituent shown two fold decrease of cytotoxicity on cancer cell lines [44]. The modi cation in the chain second amine function also changed the cytotoxicity; compounds with morpholino(propylenamino)-substituted anthraquinones were less potent that compounds with piperidino-or pyrrolidino(propylenamino)-substituted anthraquinones against leukemia P388 cells [42] and compound with piperidino-moiety were more active that the pyrrolidino-substituted one in the ovarian cancer cell lines [45]. Herein we demonstrate that 3-position amine modi cation of 1-(3-aminopropargyl)-substituent can also signi cantly potentiate the anticancer activity of hydroxyanthraquinone.…”

Section: Chemical Synthesismentioning

confidence: 99%

Synthesis, characterization and anticancer evaluation of nitrogen-substituted 1-(3-aminoprop-1-ynyl)-4-hydroxyanthraquinone derivatives

et al. 2021

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Anthraquinones are of signi cant interest due to their biological activity, coloring properties and synthetic applications. Here, we describe a mild and convenient method for modi cation of 1-ethynyl-4hydroxyanthraquinone that was obtained from the Sonogashira reaction of 1-hydroxy-4iodoanthraquinone with alkynes. The copper(I) catalyzed one-pot three component reaction (A 3 -coupling) of the new 1-ethynyl-4-hydroxyanthraquinone with secondary amines and formaldehyde was the main approach for the synthesis of nitrogen substituted 1-[3-(amino)prop-1-ynyl]-4-hydroxyanthraquinones. The in uence of different substituent in the amine on reaction rate and yield has been evaluated. The cytotoxicity of 1-ethynyl-4-hydroxyanthraquinones was evaluated using the conventional MTT assay. Among all the compounds synthesized, anthraquinone-propargylamine derivatives 28, 29, and possess most promising cytotoxic potential towards glioblastoma cancer cells; compounds 14 and 19 shown selectivity towards the prostate cancer cells DU-145, and 18, and 24 -towards breast cancer cells MCF-7. The grown inhibition on these cancer cells of 18 and 24 was comparable to those of standard drug Doxorubicin. Molecular modeling of new compounds in DNA G-quadruplex binding site was performed to help understand the observed SAR trends.

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“…22 Intermediate 5 was generated following the published procedure. 23 Anthraquinone probes 8 24 and 10 25,26 were obtained by stirring 6 or 9 respectively in neat 2-morpholinoethylamine followed by removal of excess amine and purification by flash column chromatography.…”

Section: Nemorubicinmentioning

confidence: 99%

Probing cytochrome P450 bioactivation and fluorescent properties with morpholinyl-tethered anthraquinones

Errington

Sadiq

Cosentino

et al. 2018

Bioorganic & Medicinal Chemistry Letters

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Structural features from the anticancer prodrug nemorubicin (MMDX) and the DNA-binding molecule DRAQ5™ were used to prepare anthraquinone-based compounds, which were assessed for their potential to interrogate cytochrome P450 (CYP) functional activity and localisation. 1,4-disubstituted anthraquinone 8 was shown to be 5-fold more potent in EJ138 bladder cancer cells after CYP1A2 bioactivation. In contrast, 1,5-bis((2-morpholinoethyl)amino) substituted anthraquinone 10 was not CYP-bioactivated but was shown to be fluorescent and subsequently photo-activated by a light pulse (at a bandwidth 532-587 nm), resulting in punctuated foci accumulation in the cytoplasm. It also showed low toxicity in human osteosarcoma cells. These combined properties provide an interesting prospective approach for opto-tagging single or a sub-population of cells and seeking their location without the need for continuous monitoring.

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Synthesis of aminoanthraquinone derivatives and their in vitro evaluation as potential anti-cancer drugs

Cited by 26 publications

References 36 publications

Novel polyamide amidine anthraquinone platinum(II) complexes: cytotoxicity, cellular accumulation, and fluorescence distributions in 2D and 3D cell culture models

Novel polyamide amidine anthraquinone platinum(II) complexes: cytotoxicity, cellular accumulation, and fluorescence distributions in 2D and 3D cell culture models

Synthesis, characterization and anticancer evaluation of nitrogen-substituted 1-(3-aminoprop-1-ynyl)-4-hydroxyanthraquinone derivatives

Probing cytochrome P450 bioactivation and fluorescent properties with morpholinyl-tethered anthraquinones

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