- Interaction of anthraquinone anti-cancer drugs with DNA:Experimental and computational quantum chemical study
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Anthraquinones form the basis of several anticancer drugs. Anthraquinones anticancer drugs carry out their cytotoxic activities through their interaction with DNA, and inhibition of topoisomerase II activity. Anthraquinones (AQ4 and AQ4H) were synthesized and studied along with 1,4-DAAQ by computational and experimental tools. The purpose of this study is to shade more light on mechanism of interaction between anthraquinone DNA affinic agents and different types of DNA. This study will lead to gain of information useful for drug design and development. Molecular structures were optimized using DFT B3LYP/6-31?+?G(d). Depending on intramolecular hydrogen bonding interactions two conformers of AQ4 were detected and computed as 25.667?kcal/mol apart. Molecular reactivity of the anthraquinone compounds was explored using global and condensed descriptors (electrophilicity and Fukui functions). Molecular docking studies for the inhibition of CDK2 and DNA binding were carried out to explore the anti cancer potency of these drugs. NMR and UV-VIS electronic absorption spectra of anthraquinones/DNA were investigated at the physiological pH. The interaction of the three anthraquinones (AQ4, AQ4H and 1,4-DAAQ) were studied with three DNA (calf thymus DNA, (Poly[dA].Poly[dT]) and (Poly[dG].Poly[dC]). NMR study shows a qualitative pattern of drug/DNA interaction in terms of band shift and broadening. UV-VIS electronic absorption spectra were employed to measure the affinity constants of drug/DNA binding using Scatchard analysis.
- Al-Otaibi, Jamelah S.,Teesdale Spittle, Paul,El Gogary, Tarek M.
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p. 751 - 760
(2016/09/07)
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- ANTHARQUINONE COMPOUNDS AS ANTI CANCER COMPOUNDS
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Anthraquinone compounds of the general formula (I) or a salt thereof (Formula I) in which R1 to R4 are each selected from the group consisting of H, C1-4 alkyl, X1, -NHR0N (R5)2 in which R0 is a C1-12 alkanediyl and each R5 is H or optionally substituted C1-4 alkyl, and a group of formula (II) in which at least one of R6,R7 and R8 is selected from X2 , and X2 substituted C1-4 alkyl and any others are H or C1-4 alkyl; R9 is selected from H, C1-4 alkyl, X2 and X2 substituted C1-4 alkyl; m is 0 or 1; n is 1 or 2; X1 is a halogen atom, a hydroxyl group, a C1-6 alkoxyl group, an aryloxy group or an acyloxy group; and X2 is a halogen atom, a hydroxyl group, a C1-6 alkoxyl group, an aryloxy group or an acyloxy group; provided that at least one of R1 to R4 is a group of formula (II). The N-oxides are useful prodrugs which are selectively bioreduced in hypoxic tumours to the corresponding cyclic amine derivatives. The amine compounds are cytotoxic and may be used as alkylating agents having topoisomerase II inhibiting activities in cancer therapy.
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Page/Page column 19
(2008/06/13)
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- Antitumor Agents-CLXVII. Synthesis and structure-activity correlations of the cytotoxic anthraquinone 1,4-bis-(2,3-epoxypropylamino)-9,10-anthracenedione, and of related compounds
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1,4-Bis-(2,3-epoxypropylamino)-9,10-anthracenedione (3) was synthesized in this laboratory and was found to be a potent antitumor agent. Derivatives of this compound containing anthraquinone, naphthoquinone, and quinone skeletons were also prepared and evaluated for in vitro cytotoxic activity in several cell lines. These molecules were designed as bifunctional antitumor agents with the potential to act as (1) intercalating agents due to their planar backbones, and (2) alkylating agents due to the presence of alkylating moieties in their side chains. Compounds with an anthraquinone skeleton and propylamino side chains containing epoxides or halohydrins as the alkylating species showed greater activity than similar compounds with naphthoquinone or quinone skeletons. Compounds without these alkylating functionalities (e.g., with alkene or amino groups) were generally inactive. Hydroxy substitution on the planar skeleton in conjunction with alkylating side chains gave compounds with the most potent cytotoxic activity. The position of the hydroxy groups and side chains could be varied without substantially affecting activity. Activity was retained when an epoxypropyloxy side chain was substituted for the epoxypropylamino side chain in the parent compound.
- Johnson, Mary G.,Kiyokawa, Hiroshi,Tani, Shohei,Koyama, Junko,Morris-Natschke, Susan L.,Mauger, Anthony,Bowers-Daines, Margaret M.,Lange, Barry C.,Lee, Kuo-Hsiung
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p. 1469 - 1479
(2007/10/03)
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- An improved practical synthesis of leuco-1,4,5,8-tetrahydroxyanthraquinone
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Leuco-1,4,5,8-tetrahydroxyanthraquinone was prepared from chrysazin by nitration and reduction with iron powder, followed by treatment with sodium hydrosulfite in alkaline solution. This method is suitable for scaling, and is significant and improved over literature methods.
- Chang,Cheng
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p. 1893 - 1900
(2007/10/02)
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- Liquid Crystalline Triptycene Derivatives
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A route to triptycenes substituted with one, two, five, and six paraffinic chains was developed using the Diels-Alder reaction as the key reaction. 1,4,5,8-Tetrakis(dodecyloxy)-11-hydroxy-14-(dodecanoyloxy)triptycene, 1,4,5,8-tetrakis(dodecyloxy)-11,14-bis(dodecanoyloxy)triptycene, and 1,4,5,8,11,14-hexakis(dodecyloxy)triptycene were obtained in a nine-step procedure starting from diaminoanthrarufin.The five-chain derivative demonstrates original mesomorphic properties.
- Norvez, Sophie
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p. 2414 - 2418
(2007/10/02)
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- Epitaxygens: Mesophases based on the Triptycene Molecular Subunit
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Two examples of triptycene-based epitaxygens, in which aliphatic chains and aromatic cores from symmetry compatible lamellar lattices, have been synthesized and their mesomorphic properties have been studied.
- Norvez, Sophie,Simon, Jacques
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p. 1398 - 1399
(2007/10/02)
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- Chemistry of Quinones. Part 6. The Selective Hydrolysis of α-Acetoxyanthraquinones and Related Compounds by Trifluoroacetic Acid Containing Small Amounts of Water
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Acetoxy- or benzoyloxy-substituents adjacent to the carbonyl groups of anthraquinone, 1,4-naphthoquinone, naphthacene-5,12-quinone, benzophenone, and methyl benzoate are selectively converted into hydroxy-groups by treatment with trifluoroacetic acid containing small amounts of water.In the absence of water a reversible acidolysis occurs.Water reacts with the acylating agent, thus preventing the reverse reaction.Evidence is presented that the hydrolyses are of the AAC1 type.
- Harrison, Charles R.,Hodge, Philip,Khan, Naeem
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p. 1592 - 1594
(2007/10/02)
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