Synthesis, crystal structure, DNA interaction and in vitro anticancer activity of a Cu(<scp>ii</scp>) complex of purpurin: dual poison for human DNA topoisomerase I and II

Das, Piyal; Jain, Chetan Kumar; Dey, Soma; Saha, Rajat; Chowdhury, Abhishek Dutta; Roychoudhury, Susanta; Kumar, Sanjay; Majumder, Hemanta K.; Das, Saurabh

doi:10.1039/c4ra07127a

Cited by 45 publications

(116 citation statements)

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“…For example, the derivative most closely related to the structures reported here, 1,4-dihydroxy-2-methoxy-7-methylanthracene-9,10-dione, has been isolated from two different fungi and the structure reported [refcodes GEPCOU (She et al, 2006) and GEPCOU01 (Muangsin et al, 2008)]. Complexes of purpurin with rhenium (refcodes CEVNIB, CEVNOH and AVABEF; Sathiyendiran, et al, 2006Sathiyendiran, et al, , 2011, copper [refcode ZOMSEB; Das, et al, 2014), tin (refcodes MOQTAO and MOQTES; de Sousa et al, 2009), calcium and aluminum (refcode LAYBAO; Bergerhoff & Wunderlich, 1993) have been reported. In each of the reported structures, those compounds with a free hydroxyl group flanking the anthraquinone carbonyl also exhibit the intramolecular hydrogen bond reported for (1) and (2).…”

Section: Database Surveymentioning

confidence: 99%

Synthesis and crystal structures of two purpurin derivatives: 1,4-dihydroxy-2-propoxyanthraquinone and 2-butoxy-1,4-dihydroxyanthraquinone

Bosch

McClain

2017

Acta Cryst E

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The title compounds were obtained by deprotonation of 1,2,4-trihydroxyanthraquinone (purpurin) using sodium hydride followed by reaction with either 1-bromopropane or 1-bromobutane. 1,4-Dihydroxy-2-propoxyanthraquinone crystallizes as a 1:1 solvate from acetonitrile, C 17 H 14 O 5 ÁCH 3 CN. The anthraquinone core of the molecule is essentially planar and both hydroxy groups participate in intramolecular O-HÁ Á ÁO (carbonyl) hydrogen bonds. The propyl chain is angled slightly above the plane of the anthraquinone moiety with a maximum deviation of 0.247 (2) Å above the plane for the terminal carbon atom. In contrast, 2-butoxy-1,4-dihydroxyanthraquinone, C 18 H 16 O 5 , crystallizes from nitromethane with two independent molecules in the asymmetric unit. The anthraquinone core of each independent molecule is essentially planar and both hydroxy groups on both molecules participate in intramolecular O-HÁ Á ÁO(carbonyl) hydrogen bonds. The butyl chain in one molecule is also angled slightly above the plane of the anthraquinone moiety, with a maximum deviation of 0.833 (5) Å above the plane for the terminal carbon atom. In contrast, the butyl group on the second molecule is twisted out of the plane of the anthraquinone core with a torsion angle of 65.1 (3), resulting in a maximum deviation of 1.631 (5) Å above the plane for the terminal carbon atom. Chemical contextPurpurin, 1,2,4-trihydroxy anthraquinone, is a major component of the dye extracted from madder root (Schweppe & Winter, 1997). The extract from madder root has been used to dye wool and other fabrics since antiquity. Purpurin is commercially available and we here report two derivatives, 1,4-dihydroxy-2-propoxy anthraquinone and 2-butoxy-1,4-dihydroxy anthraquinone, prepared by selective deprotonation of purpurin followed by alkylation with the either 1-bromopropane or 1-bromobutane. Structural commentaryThe asymmetric unit of 1,4-dihydroxy-2-propoxy anthraquinone (1), crystallized from acetonitrile solvent, contains a single anthraquinone molecule and one acetonitrile solvate molecule as shown in Fig. 1. The two intramolecular hydrogen bonds (Table 1) are typical for the 1,4-dihydroxy anthraquinones and 1-hydroxyanthraquinones. These hydrogen bonds are maintained in chloroform solution, as shown by the chemical shift of 13.47 and 13.56 ppm for the two hydroxyl protons. The anthraquinone moiety is planar, with an average root mean square (r.m.s.) deviation of atoms C1 to C14 of 0.021 Å , in which the maximum deviation from the plane defined by atoms C1 to C14 is 0.044 (1) Å for C9. The propyl chain is angled slightly above the plane of the anthraquinone moiety, with deviations of 0.043 (2), 0.143 (2) and 0.247 (2) Å for atoms C15, C16 and C17, respectively, from the plane defined by atoms C1-C14. The acetonitrile is angled towards H10 with a N1Á Á ÁC10 distance of 3.401 (2) Å . The final difference map shows several peaks of 0.2 to 0.7 e Å À3 in the anthraquinone plane that suggest the presence of minor whole-molecule disorder in which the anthraquinone is ...

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Section: Database Surveymentioning

confidence: 99%

Synthesis and crystal structures of two purpurin derivatives: 1,4-dihydroxy-2-propoxyanthraquinone and 2-butoxy-1,4-dihydroxyanthraquinone

Bosch

McClain

2017

Acta Cryst E

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“…[9][10][11][12][13][14][15] In the process, the anticancer agent linked to the metal ion is able to enter the cancer cell much more easily than on its own and can then initiate cell damage, thus showing anticancer activity. [16][17][18] Once within the cell, this happens for the anticancer agent in a state bound to the metal ion or by dissociating from it inside the cell. 16 Thus, by using a copper complex of an anticancer agent, the cell can be tempted to procure copper ions, thereby in the process assimilating the anticancer agent that will eventually kill it by disturbing one or more of the cellular pathways that help these cells to survive.…”

Section: -12mentioning

confidence: 99%

“…[16][17][18] Once within the cell, this happens for the anticancer agent in a state bound to the metal ion or by dissociating from it inside the cell. 16 Thus, by using a copper complex of an anticancer agent, the cell can be tempted to procure copper ions, thereby in the process assimilating the anticancer agent that will eventually kill it by disturbing one or more of the cellular pathways that help these cells to survive. [16][17][18]20 Besides, the complexes have various other attributes that are most oen not known for the ligand (the anticancer agent).…”

Section: -12mentioning

confidence: 99%

“…16 Thus, by using a copper complex of an anticancer agent, the cell can be tempted to procure copper ions, thereby in the process assimilating the anticancer agent that will eventually kill it by disturbing one or more of the cellular pathways that help these cells to survive. [16][17][18]20 Besides, the complexes have various other attributes that are most oen not known for the ligand (the anticancer agent). Owing to this, their efficacy far exceeds that of the anticancer agent itself.…”

Section: -12mentioning

confidence: 99%

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Cu^IIcomplex of emodin with improved anticancer activity as demonstrated by its performance on HeLa and Hep G2 cells

Mandal

Singha

Dey³

et al. 2017

RSC Adv.

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Emodin, a hydroxy-9,10-anthraquinone, resembles anthracycline anticancer drugs at the core and possesses anticancer activities. A Cu II complex of emodin [Cu II (emod) 2 ] 2À was synthesized and its crystal structure wasdetermined by Rietveld refinement of the PXRD data by using an appropriate structural model based on spectroscopy. This is the third report on the crystal structure of a hydroxy-9,10-anthraquinone with a 3d-transition metal ion. Since the formation of reactive oxygen species (ROS) by anthracycline-based anticancer drugs is important for antitumor activity and given the fact that the generation of ROS is responsible for cardiotoxic side effects, it is essential to be able to control their formation. Complex formation decreases ROS generation and could thereby lead to a decrease in cardiotoxic side effects. However, in an attempt to decrease complications, there is also the possibility of compromising the therapeutic efficacy. For this reason, the activities of emodin and its modified form [Cu(II) complex] were studied on the carcinoma cell lines HeLa and Hep G2 to see how they compared with each other in terms of performance. Studies were also performed on WI 38 lung fibroblast normal cells. The studies revealed that, in spite of the decreased ROS formation, followed by the DCFDA assay, the Cu(II) complex showed better activity on carcinoma cell lines. This suggests that the complex has other attributes that enable it to perform better than emodin. Consequently, one such attribute, namely DNA binding, was thoroughly investigated by varying the ionic strength and the temperature of the medium. It was found that the complex was able to bind DNA better than emodin, and, more importantly, since both generate a good amount of anionic species in solution under increased ionic strength of the medium, both bind DNA better; the increase in binding with increase in ionic strength being higher for the complex. The study suggests that with a substantial decrease in ROS generation by the complex, there are likely to be less toxic side effects, which is a key advantage of the complex, leading to an improvement in the therapeutic index. The complex showed almost no activity on WI 38 normal cells.

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“…However, as cisplatin selectively attacks squamous cells, much more attention was devoted to anthracycline drugs, particularly doxorubicin (Dox) which exhibits a broader spectrum of activity [33,34]. Purpurin (Purp) displays a similar activity to Dox [35]. It is an active compound in photodynamic therapy [36] and demonstrates an ability to inhibit topoisomerase II as well as intercalate DNA [37].…”

Section: Introductionmentioning

confidence: 99%

Hybrids of Iron-Filled Multiwall Carbon Nanotubes and Anticancer Agents as Potential Magnetic Drug Delivery Systems: In Vitro Studies against Human Melanoma, Colon Carcinoma, and Colon Adenocarcinoma

Boncel

Pluta

Skonieczna

et al. 2017

Journal of Nanomaterials

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Cell type, morphology, and functioning are key variables in the construction of efficient "drug-vehicle" hybrids in magnetic drug delivery. Iron-encapsulated multiwall carbon nanotubes (Fe@MWCNTs) appear as promising candidates for theranostics due to in situ chemical catalytic vapor deposition (c-CVD) synthesis, straightforward organic functionalization, and nanoneedle (1D) behavior. Here, model hybrids were synthesized by exploring C-sp 2 chemistry ((1+2)-cycloaddition of nitrenes and amidation) of the outer MWCNT walls combined with anticancer agents, that is, 5-fluorouracil (5FU), purpurin (Purp), and 1,8-naphthalimide DNA intercalators (NIDIs), via linkers. Analyses of the Fe@MWCNT vehicles by SEM, TEM, and Raman spectroscopy revealed their morphology while Mössbauer spectroscopy confirmed the presence of encapsulated ferromagnetic iron-based nanodomains. Cytotoxicity of the hybrids was studied using a 24 h MTS assay combined with the apoptosis and life cycle assays against human melanoma (Me45), colon carcinoma (HCT116+), and colon adenocarcinoma (Caco-2). The cells had different sensitivity to the vehicles themselves as well as to the hybrids. MWCNT-based covalent hybrids of 5FU and Purp emerged as the most promising systems against Me45 and HCT116+ cell lines with the highest in vitro cytotoxicity and proapoptotic activity. Furthermore, nanotubes bearing 4-nitro-and 4-(N-morpholinyl)-1,8-naphthalimide DNA intercalators appear as a promising candidate for the treatment of Caco-2.

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Synthesis, crystal structure, DNA interaction and in vitro anticancer activity of a Cu(ii) complex of purpurin: dual poison for human DNA topoisomerase I and II

Abstract: Although generation of reactive oxygen species (ROS) by anthracycline anticancer drugs is essential for anti-tumor activity, they make these drugs cardiotoxic.

Cited by 45 publications

References 48 publications

Synthesis and crystal structures of two purpurin derivatives: 1,4-dihydroxy-2-propoxyanthraquinone and 2-butoxy-1,4-dihydroxyanthraquinone

Synthesis and crystal structures of two purpurin derivatives: 1,4-dihydroxy-2-propoxyanthraquinone and 2-butoxy-1,4-dihydroxyanthraquinone

Cu^IIcomplex of emodin with improved anticancer activity as demonstrated by its performance on HeLa and Hep G2 cells

Hybrids of Iron-Filled Multiwall Carbon Nanotubes and Anticancer Agents as Potential Magnetic Drug Delivery Systems: In Vitro Studies against Human Melanoma, Colon Carcinoma, and Colon Adenocarcinoma

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Synthesis, crystal structure, DNA interaction and in vitro anticancer activity of a Cu(ii) complex of purpurin: dual poison for human DNA topoisomerase I and II

Abstract: Although generation of reactive oxygen species (ROS) by anthracycline anticancer drugs is essential for anti-tumor activity, they make these drugs cardiotoxic.

Cited by 45 publications

References 48 publications

Synthesis and crystal structures of two purpurin derivatives: 1,4-dihydroxy-2-propoxyanthraquinone and 2-butoxy-1,4-dihydroxyanthraquinone

Synthesis and crystal structures of two purpurin derivatives: 1,4-dihydroxy-2-propoxyanthraquinone and 2-butoxy-1,4-dihydroxyanthraquinone

CuIIcomplex of emodin with improved anticancer activity as demonstrated by its performance on HeLa and Hep G2 cells

Hybrids of Iron-Filled Multiwall Carbon Nanotubes and Anticancer Agents as Potential Magnetic Drug Delivery Systems: In Vitro Studies against Human Melanoma, Colon Carcinoma, and Colon Adenocarcinoma

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Cu^IIcomplex of emodin with improved anticancer activity as demonstrated by its performance on HeLa and Hep G2 cells