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Interaction of metal ions with biologically active molecules like 5-nitroimidazoles modulates their electronic environment and therefore influences their biological function. In the present work, an antiparasitic drug tinidazole (tnz) was selected and a Cu(II) complex of tnz [Cu2(OAc)4(tnz)2] was prepared. A dinuclear paddle-wheel [Cu2(OAc)4(tnz)2] was obtained by single-crystal XRD and further characterized by spectroscopic techniques and cyclic voltammetry. To understand the biological implications of complex formation, interaction of tnz and its complex was studied with calf thymus DNA, bacterial and fungal cell lines. Results of calf thymus DNA interaction using cyclic voltammetry indicate the overall binding constant (K*) of Cu2(OAc)4(tnz)2[(59 ± 6) × 104 M−1] is ~17 times greater than that of tnz [(3.3 ± 0.4) × 104 M−1]. Minimum inhibitory concentration values suggest that [Cu2(OAc)4(tnz)2] possesses better antibacterial activity than tnz on both bacterial strains, while the activity on a fungal strain was comparable. Tinidazole, a 5-nitroimidazole is active on protozoan and bacterial infections. This study made an attempt to see if a Cu(II) complex of tinidazole had comparable efficacy on chosen bacteria and fungi. The prepared complex was characterized by XRD, spectroscopy, elemental analysis cyclic voltammetry. DNA interaction was studied using cyclic voltammetry and fitted by non-linear analysis. [ABSTRACT FROM PUBLISHER]

Hydroxy-9,10-anthraquinones resemble anthracycline-based anticancer drugs. By varying the pH of the solution, the proton dissociation constants of 1,2,5,8-tetrahydroxy-9,10-anthraquinone (THAQ) were determined. Interaction of THAQ with calf thymus DNA (ct DNA) was studied by UV-Vis spectroscopy to determine the overall binding constant and site size of interaction. The binding constant values (~104) for THAQ interacting with ct DNA at different pH were an order less than that known for anthracyclines. From knowledge of the overall binding constants at different pH values and the first pK of THAQ, the contribution of each form (neutral and monoanionic) towards overall binding with ct DNA could be obtained under physiological conditions. Hence, knowing the contributions of the neutral and monoanionic forms, it now becomes possible to know the overall binding constant for an interaction of THAQ with ct DNA at any pH. The calculated parameters help in understanding the role of the negative charge on the monoanionic form during interaction and suggests suitable chemical modifications that could prevent the development of such negative charges. This could lead to an increase in binding of THAQ to ct DNA. The study also helps to recognize the importance of sugar units in anthracycline anticancer drugs in DNA interaction. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Anthracyclines are broad-spectrum antibiotics that are used against several human cancers. Hydroxy-9,10-anthraquinone compounds closely resemble anthracycline antibiotics from a structural and functional viewpoint. High cost and aspects of toxicity introduce limitations on its use. On complex formation the toxicities of anthracyclines decrease. A close analogue is sodium 1,4-dihydroxy-9,10-anthraquinone-2-sulphonate (AS), which is a comparatively cheaper molecule and resembles a good number of anthracycline derivatives. It forms a complex with CuII, [Cu(AS)2]. The complex interacts with calf thymus DNA that was studied by UV/Vis spectroscopy and cyclic voltammetry. The experimental data obtained from the two techniques was analyzed for binding constant and size of the binding site. These results not only corroborate each other but also justify earlier data obtained using fluorescence spectroscopy. An important aspect to this study was that nonlinear curve fitting, which is usually applied for analyzing DNA interaction using fluorescence and absorption spectroscopy, was used for the first time to analyze the interaction of the complex with DNA using cyclic voltammetry by monitoring the change in the reduction peak current ( Ip). The DNA binding data provides an insight into a probable mode of action of the hydroxy-9,10-anthraquinones within cells as modification of DNA that leads to cell death is an important aspect in cancer research. [ABSTRACT FROM AUTHOR]

The anthracycline drug adriamycin and its metal complexes are efficient in treating several forms of human cancers with recognized antineoplastic activity attributed to strong interactions with DNA within the target cells. The hydroxy-9,10-anthraquinone unit present in the molecule controls and regulates drug action. Metal ions when linked to adriamycin help to reduce the generation of radicals responsible for toxic side effects. A complex of adriamycin with Ni(II) was prepared and its physicochemical characteristics and DNA-binding ability were compared to a Ni(II) complex of sodium-1,4-dihydroxy-9,10-anthraquinone-2-sulphonate (NaLH2), an analog of adriamycin. Interactions with calf thymus DNA of both complexes were studied by UV-Vis and fluorescence spectroscopy. Binding parameters determined for both complexes agree with each other. Binding of the Ni(II)-adriamycin complex to DNA was five to eight times stronger than for the Ni(II) complex of the hydroxy-9,10-anthraquinone analog, Na2[Ni(NaLH)2Cl2] · 2H2O, i.e., Ni(NaLH)2. The difference in binding was attributed to the presence of sugar units in adriamycin and to its absence in NaLH2. Although the Ni(II) complex of the hydroxy-9,10-anthraquinone analog of adriamycin [Ni(NaLH)2] was slightly weaker in binding DNA than the drug and its Ni(II) complex, a much lower cost of the former justifies its consideration as a substitute for the anthracycline drugs that are now in use. [ABSTRACT FROM PUBLISHER]

Anthracycline drugs show anticancer activity, an ability to inhibit DNA replication and RNA transcription but are costly. This study attempts to see if cheaper hydroxy-9,10-anthraquinones (1,2,4-trihydroxy-9,10-anthraquinone) that structurally resemble anthracyclines mimic its biological interactions and whether it can be a suitable substitute. Proton dissociation at 298 K for THA, pK1 = 4.82 ± 0.05 (phenolic OH at C2) and particularly pK2 = 9.22 ± 0.05 (phenolic OH at C1 and C4) closely resemble those of the anthracyclines. THA undergoes a single step two-electron reduction in aqueous media (pH 7.36) having E1/2 = −0.69 V and two successive single-electron reduction in DMF having E1/2 values −0.70 V and −1.06 V, respectively. CV data showed quasi-reversible nature of THA in aqueous media. E1/2 values of THA were comparable to anthracycline drugs suggesting similarity in redox behavior. Binding studies of THA to ct DNA using UV-Vis and fluorescence spectroscopy were analyzed. Intrinsic binding constant and site size of interaction were (4.80 ± 0.2) × 104 M−1 and (5.96 ± 0.3) bases, respectively. THA, approximately three to five times weaker in binding ct DNA than anthracycline anticancer drugs suggests a role for sugar moieties present in anthracyclines. Anti-leukemic activity studies of THA on cultured MOLT-4 cell lines were performed and apoptosis measured by MTT assay. Result indicates THA to be a potent inducer of apoptosis in MOLT-4 cell line having an IC50 value of 33.8 µM. THA therefore possesses anti-leukemic activity that is comparable to anthracyclines on P388 leukemia and the study reveals that 1,2,4-trihydroxy-9,10-anthraquinone to be a suitable substitute to the costlier anthracyclines. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The anthracycline drugs, adriamycin and daunorubicin, efficient in the treatment of various human cancers, form strong intercalation complexes with DNA. The therapeutic efficiency and toxic properties of the drugs are associated with electron transfer processes, which correlate well with the redox behaviour of the compounds. Sodium 1,4-dihydroxy 9,10-anthraquinone-2-sulphonate (sodium quinizarin-2-sulphonate, NaLH2) (Na-Qz-2S) is a molecule that resembles anthracycline drugs and has a simpler structure in comparison to these drugs. Two electrons in the course of chemical action reduce this molecule like the anthracyclines. Electrochemical methods were used to identify this process. UV-Vis and fluorescence spectroscopy were used to analyse binding of the compound to calf thymus DNA. The binding constant and site size were evaluated for Na-Qz-2S and the same compared to that of the anthracyclines. Such comparisons are essential in order to understand whether the simpler hydroxy-anthraquinones can be a substitute for anthracycline drugs in cancer chemotherapy. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Copper(II) forms a complex with sodium 1,4-dihydroxy-9,10-anthraquinone-2-sulphonate (sodium quinizarin-2-sulphonate, NaQSH2), an analogue of the core unit of anthracycline antibiotics used in the treatment of cancer. The 1:2 metal–ligand complex is formed in aqueous solution at neutral and acidic pH while in alkaline pH both 1:1 and 1:2 species are formed. The effective stability constant of the 1:2 metal–ligand complex is 9.64×1016 while that of the 1:1 metal–ligand complex is 9.4×109. The 1:2 complex Cu(NaQSH)2(H2O)2 was synthesized and characterized by different techniques in solid state and in solution. The complex Cu(NaQSH)2(H2O)2 interacts with calf thymus DNA which was studied by fluorescence spectroscopy. The binding constant and site size for the interaction with DNA were determined. [Copyright &y& Elsevier]

Abstract: Ionizing radiation when allowed to fall upon cells or DNA, the radicals produced modify the base-pair region of the double strands. Radiation-induced double-strand modifications in calf thymus DNA were detected using Ni(II) and Fe(III) complexes of 1,2 dihydroxy 9,10 anthraquinone (DHA). 60Co was used as the source for γ-radiation and ethidium bromide (EB) as the fluorescent dye for detecting double-strand modifications caused in DNA. Results show that the Fe(III)–DHA complex is more efficient in modifying the base-pair region in double-stranded DNA in comparison to DHA or the Ni(II)–DHA complex. [Copyright &y& Elsevier]

There is enough proof to believe that free-radical intermediates of anthracycline based anticancer agents are involved in different stages of drug action. Subtle therapeutic differences observed in the actions of different anthracyclines largely influence the mechanism of action of the drugs that distinguish one member from another. Redox properties control biological responses related either to the one-electron quinone/semiquinone couple or the two-electron quinone/quinone-dianion couple. Comproportionation also leads to generation of semiquinone. Hence, whatever the form of reduction of the quinone moiety, a substantial amount of semiquinone is eventually formed in the system. Immediately after formation, there is competition between natural radical-decay pathways and one-electron transfer reactions that generate the superoxide-radical anion. Prototropic properties control rate of radical decay while redox properties control rate of electron transfer to molecular oxygen. In aerated medium, semiquinone-radical anion and superoxide-radical anion co-exist while in de-aerated medium semiquinone-radical anion predominates. All the radicals are damaging to the biological system. Through this study, attempt was made to detect changes induced by the radicals on pyrimidine based nucleic acid bases and calf thymus DNA in aerated and de-aerated (Ar saturated) medium to know the mechanism by which Emodin, its CuII/MnII complexes might affect DNA. Semiquinone-radical anion was generated electrochemically maintaining a glassy carbon electrode at the first reduction potential of each compound. Since the chosen compound (Emodin), its complexes are analogues of anthracyclines, findings on them can be extrapolated to understand the differences in anticancer activity or of adverse drug reactions reported in an innumerable number of clinical studies related to anthracyclines where the difference in structure of different members is due to differences in the relative positioning of hydroxy groups on the hydroxy-9, 10-anthraquinone moiety of anthracyclines. The study helps to realize action of compounds of this class as anticancer agents. Image 108205 • Action of anthracyclines is due to one-electron quinone/semiquinone or two-electron quinone/dianion. • Semiquinone-radical anion was generated electrochemically using glassy carbon electrode. • Study detects changes caused by radicals on pyrimidine nucleic acid bases and calf thymus DNA. • Semiquinone on Emodin in de-aerated medium was most effective on pyrimidine nucleic acid bases. • The CuII complex of Emodin was most effective in aerated medium attributed to Fenton reactions. [ABSTRACT FROM AUTHOR]

Two new copper(II) complexes, [Cu(L)(OCN)] (1) and [CuL(dca)]n (2), where HL = 2-(-(2-(diethylamino)ethylimino)methyl)naphthalen-1-ol, dca = N(CN)2-, have been synthesized and characterized by elemental analysis, IR, UV-VIS spectroscopy and single crystal X-ray diffraction studies. Complex 1 has square planar and complex 2 square pyramidal geometries in solid state around metal centre. Interactions of the complexes with calf thymus DNA (CT DNA) were studied by UV-VIS spectroscopy. Binding constant and site size of interaction were determined. Binding site size and intrinsic binding constant K revealed complex 1 interacted with calf thymus DNA better than complex 2. [CuL(dca)]n (2), where HL = 2-(-(2-(diethylamino)ethylimino)methyl)naphthalen-1-ol, dca = N(CN)2-, have been synthesized and characterized by elemental analysis, IR, UV-VIS spectroscopy and single crystal X-ray diffraction studies. Complex 1 has square planar and complex 2 square pyramidal geometries in solid state around metal centre. Interactions of the complexes with calf thymus DNA (CT DNA) were studied by UV-VIS spectroscopy. Binding constant and site size of interaction were determined. Binding site size and intrinsic binding constant K revealed complex 1 interacted with calf thymus DNA better than complex 2. [ABSTRACT FROM AUTHOR]

Quinalizarin, an analogue of anthracycline anticancer agents, is an anticancer agent itself. A CuII complex was prepared and characterized by elemental analysis, UV-Vis & IR spectroscopy, mass spectrometry, EPR and DFT. The intention behind the preparation of the complex was to increase cellular uptake, compare its binding with DNA against that of quinalizarin, modulation of semiquinone formation, realization of human DNA topoisomerase I & human DNA topoisomerase II inhibition and observation of anticancer activity. While the first two attributes of complex formation lead to increased efficacy, decrease in semiquinone generation could results in a compromise with efficacy. Inhibition of human DNA topoisomerase makes up this envisaged compromise in free radical activity since the complex shows remarkable ability to disrupt activities of human DNA topoisomerase I and II. The complex unlike quinalizarin, does not catalyze flow of electrons from NADH to O 2 to the extent known for quinalizarin. Hence, decrease in semiquinone or superoxide radical anion could make modified quinalizarin [as CuII complex] less efficient in free radical pathway. However, it would be less cardiotoxic and that would be advantageous to qualify it as a better anticancer agent. Although binding to calf thymus DNA was comparable to quinalizarin, it was weaker than anthracyclines. Low cost of quinalizarin could justify consideration as a substitute for anthracyclines but the study revealed IC 50 of quinalizarin/CuII-quinalizarin was much higher than anthracyclines or their complexes. Even then, there is a possibility that CuII-quinalizarin could be an improved and less costly form of quinalizarin as anticancer agent. Synopsis: A CuII complex of quinalizarin was prepared with the intention of increasing cellular uptake, study binding with DNA, modulate formation of semiquinone and check for inhibition of human DNA topoisomerase I and II to correlate observed anticancer activity. Low cost of quinalizarin justifies its consideration as a substitute for anthracyclines. [Display omitted] • Quinalizarin (THAQ), an analogue of anthracyclines, is active pharmacologically. • Complex formation modulates generation of free radicals that affect its mechanism of action. • The complex is an efficient inhibitor of topoisomerase enzymes, crucial for drug action. • Interaction of [CuII(THAQ) 2 (H 2 O) 2 ] with topoisomerase was realized by molecular docking. • THAQ, the acetylated form, shows more efficacy on ALL MOLT 4 cells than [CuII(THAQ) 2 (H 2 O) 2 ]. [ABSTRACT FROM AUTHOR]