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.

The formation of reactive oxygen species (ROS) by anthracycline anticancer drugs is essential for its antitumor activity but they also make these drugs cardiotoxic. When complexed with metal ions there is a decrease in ROS formation and therefore in cardiotoxicity. Interestingly, inspite of producing fewer ROS, some of the complexes are effective antitumor agents, often better than the parent anthracycline. Purpurin (LH 3 ), a hydroxy-9, 10-anthraquinone, resembles doxorubicin at the core. An Mn II complex of LH 3 [Mn II (LH 2 ) 2 ] was synthesized to see the extent to which the complex resembles metal-anthracyclines with regard to structure and function. Crystal structure was determined by Rietveld refinement of PXRD data using an appropriate structural model developed on the basis of spectroscopic information. This being only the second report on the crystal structure of a hydroxy-9,10-anthraquinone with a 3d-transition metal ion. Bond lengths, bond angles were obtained by structural refinement.The structure is supported by DFT calculations. DNA binding of the complex is slightly better than purpurin but more importantly unlike purpurin, the binding constant values remained constant even with an increase in the pH of the medium. The NADH dehydrogenase assay and the DCFDA-ROS generation assay showed that generation of superoxide in the former and ROS in general in the latter were significantly less for the complex than for purpurin. Even with decreased ROS formation, the complex is able to maintain the biological activity of purpurin. occurs through sequential one-electron transfer steps, generating Mn(III) intermediates. [45][46][47] . Thus for this study, an Mn(II) complex of 1,2,4-trihydroxy-9,10-anthraquinone (purpurin) was prepared and some of its parameters compared with known metal complexes of anthracyclines or hydroxy-9,10anthraquinones. 12,14,15,[20][21][22][23] Purpurin (1, 2, 4 trihydroxy-9,10-anthraquinone) resembling the core of anthracyclinesThe novel aspects of this study are the structure of the complex obtained from powder X-ray diffraction data since single crystals were not obtained, determination of thermodynamic parameters pertaining to interaction of purpurin and its complex with calf thymus DNA and lack of stimulated ROS formation by the complex. The structure is novel since the same is rare for metal complexes of hydroxy-9,10-anthraquinones, with only one report so far from single crystal X-ray diffraction. 48 This is only the second structure of a metal complex of a hydroxy-9,10-anthraquinone with a 3d transition metal ion. 14 The importance of the thermodynamic study is that it helps to explain trends observed in binding of a hydroxy-9,10-anthraquinone and its metal complex with DNA that puts our results in proper perspective with that of established anthracyclines and their metal complexes. Decrease in ROS generation by the complex is important for it indicates that the complex is likely to be less cardiotoxic.

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The X-ray diffraction and spectroscopic properties of 1-amino-4-hydroxy-9,10-anthraquinone (1-AHAQ), a simple analogue of anthracycline chemotherapeutic drugs were studied by adopting experimental and computational methods. The optimized geometrical parameters obtained from computational methods were compared with the results of X-ray diffraction analysis and the two were found to be in reasonably good agreement. X-ray diffraction study, Density Functional Theory (DFT) and natural bond orbital (NBO) analysis indicated two types of hydrogen bonds in the molecule. The IR spectra of 1-AHAQ were studied by Vibrational Energy Distribution Analysis (VEDA) using potential energy distribution (PED) analysis. The electronic spectra were studied by TDDFT computation and compared with the experimental results. Experimental and theoretical results corroborated each other to a fair extent. To understand the biological efficacy of 1-AHAQ, it was allowed to interact with calf thymus DNA and human breast adino-carcinoma cell MDA-MB-231. It was found that the molecule induces apoptosis in this adinocarcinoma cell, with little, if any, cytotoxic effect in HBL-100 normal breast epithelial cell.