For the first time, interaction between non-toxic anthraquinone morindone with both natural and synthetic DNA duplexes has been demonstrated in this paper. Detailed analyses of the binding of morindone with DNA via UV-vis, FTIR, and circular dichroism spectroscopies were carried out. In addition, bioinformatics tools have been employed to scrutinize the binding of the dye with DNA in silico. Results represent morindone to be a better binder with a score of -5.79 compared to EtBr (known mutagenic intercalator) recorded at -5.02. Further interaction is accentuated by the microscope-assisted evidence of nuclear specific staining of tissues by morindone. The electrophoretic analysis reveals the efficacy endowed within morindone dye in rendering protection to DNA exposed to H2O2 damage and thereby conferring it safe to the nucleic acid. As DNA is often the target for majority of anticancer and antibiotic drugs, study on the interaction between molecules like morindone and DNA has relevance and implications in several biological applications including cancer therapy. Thus, we propose that morindone can also be harnessed as a diagnostic probe for DNA structure in addition to DNA-directed therapeutics. © Springer Science+Business Media, LLC 2012.

Siva R

Department of Biotechnology

School of Bio Sciences and Technology

Vellore Campus

Bhakta D

Vellore Institute of Technology (VIT) is a private university located in&nbsp;Tamil Nadu, India. Founded in 1984, as Vellore Engineering College, the institution offers 20 undergraduate, 34 postgraduate, four integrated and four research programs. It has campuses in Vellore, Amravati, Bhopal and Chennai.

VIT is one of the top ranked private universities in India according to NIRF, THE and QS Rankings.&nbsp;Govt. of India has recognized&nbsp;VIT, Vellore as an&nbsp;Institution of Eminence. This has allowed VIT to take independent quality initiatives and move up in world ranking.

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VIT University

Applied Biochemistry and Biotechnology

A series of calothrixin B (2) analogues bearing substituents at the 'E' ring and their corresponding deoxygenated quinocarbazoles lacking quinone unit were synthesized. The cytotoxicities of calothrixins 1, 2, and 15b-p and quinocarbazole analogues were investigated against nine cancer cell lines. The quinocarbazoles 21a and 25a inhibited the catalytic activity of human topoisomerase II. The plasmid DNA cleavage abilities of calothrixins 1, 2, and 15b-p identified compound 15h causing DNA cleavage comparable to that of calothrixin A (1). Calothrixin A (1), 3-fluorocalothrixin 15h and 4-fluoroquinocarbazole 21b induced extensive DNA damage followed by apoptotic cell death. Spectral and plasmid unwinding studies demonstrated an intercalative mode of binding for quinocarbazoles. We identified two promising drug candidates, the 3-fluorocalothrixin B 15h with low toxicity in animal model and its deoxygenated derivative 4-fluoroquinocarbazole 21b as having potent cytotoxicity against NCI-H460 cell line with a GI 50 of 1 nM. © 2018 American Chemical Society.

Journal of Medicinal Chemistry

Synthesis and Biological Evaluation of Calothrixins B and their Deoxygenated Analogues

Mononuclear and dinuclear copper(II) complexes with thiophenecarboxylic acid, [Cu(3-TCA)2(2,2′-bpy)] (1), [Cu(3-Me-2-TCA)2(H2O)(2,2′-bpy)] (2), [Cu(5-Me-2-TCA)2(H2O)(2,2′-bpy)] (3) and [Cu2(2,5-TDCA)(DMF)2(H2O)2(2,2′-bpy)2](ClO4)2 (4) (where 3-TCA = 3-thiophenecarboxylic acid; 3-Me-2-TCA = 3-methyl-2-thiophenecarboxylic acid; 5-Me-2-TCA = 5-methyl-2-thiophenecarboxylic acid; 2,5-TDCA = thiophene-2,5-dicarboxylic acid; 2,2′-bpy = 2,2′-bipyridyl; DMF = N,N-dimethylformamide), were synthesized. Compounds 1–4 were extensively characterized using both analytical and spectroscopic methods. Additionally, the solid-state structures of 1 and 4 were unambiguously established from single-crystal X-ray diffraction studies. The hexacoordinated Cu(II) centre in 1 (CuO4N2) is a distorted octahedral geometry whereas the pentacoodinated 4 (CuO3N2) has distorted square pyramidal geometry. Compounds 1 and 4 exhibit intermolecular hydrogen bonding which leads to the formation of two- and three-dimensional supramolecular architectures, respectively. Spectrophotometric and computational investigations suggest that these compounds bind with DNA in minor groove binding such that Kb = 4.9 × 10⁵ M⁻¹ and Ksv = 3.4 × 10⁵ M⁻¹, and binding score of −5.26 kcal mol⁻¹. The binding affinity of these complexes to calf thymus DNA is in the order 2 &gt; 3 &gt; 4 &gt; 1. Methyl-substituted thiophene ring increases the DNA binding affinity whereas unsubstituted thiophene ring DNA binding rate is reduced. The methyl group on the thiophene ring would sterically hinder π–π stacking of the ring with DNA base pairs, and subsequently they are involved in hydrophobic interaction with the DNA surface rather than partial intercalative interaction. Compounds 1–4 show pronounced activity against B16 mouse melanoma skin cancer cell lines as measured by MTT assay yielding IC50 values in the micromolar concentration range. The compounds could prove to be efficient anti-cancer agents, since at a concentration as low as 2.1 μg ml⁻¹ they exerted a significant cytotoxic effect in cancer cells whereas cell viability was not affected in normal cells.

Applied Organometallic Chemistry

Synthesis and structural and DNA binding studies of mono‐ and dinuclear copper(II) complexes constructed with ─O and ─N donor ligands: Potential anti‐skin cancer drugs

A new series of bis-pyrazoles 6a-t were synthesized from 3,5-dimethyl pyrazole using sequential approach. All these compounds were characterized by IR, 1H NMR, 13C NMR and mass spectral data. The interaction of newly synthesized bis-pyrazoles with DNA was investigated through molecular docking and absorption spectroscopic technique. Among all bis-pyrazoles compounds, the 6h compound showed lower conformational energy through in silico analysis. The interaction of each molecule in this series 6a-t with the various concentrations of DNA was examined through the UV–visible spectroscopic studies. The UV–visible spectroscopy studies on the specific binding of compound 6a, 6b, 6g, 6h, 6d, 6i, 6k, 6n, 6s with DNA have exhibited spectral shifts and the results were discussed. In further the compounds 6a-t were subjected to the in-vitro cytotoxicity studies against human pancreatic adenocarcinoma, human non-small cell lung carcinoma cell lines. Among the screened compounds, N-(3-isopropoxy-1-isopropyl-4-(3,5-dimethyl-1H-pyrazol-1-yl)-1H-pyrazol-5-yl)cyclobutane carboxamide and N-(5′-Isopropoxy-2′-isopropyl-3,5-dimethyl-2′H-[1,4′] bipyrazolyl-3′-yl)-dimethane sulfonamide were found as lead molecules since they have exhibited promising activity against both the cancer cell lines used in this study, whereas the compounds 4-(trifluoromethyl)-N-(3-isopropoxy-1-isopropyl-4-(3,5-dimethyl-2H-pyrrol-2-yl)-1H-pyrazol-5-yl)benzamide and 2,6-difluoro-N-(3-isopropoxy-1-isopropyl-4-(3,5-dimethyl-2H-pyrrol-2-yl)-1H-pyrazol-5-yl) benzamide were found to be active against the pancreatic cell line only. Rest all the other compounds were found to exhibit moderate to good activity towards both the cell lines. © 2017 Elsevier B.V.

Journal of Photochemistry and Photobiology B: Biology

Synthesis, DNA binding and in-vitro cytotoxicity studies on novel bis-pyrazoles

Catechin, a yellow colored molecule obtained from the wood of Acacia catechu was analyzed for its interaction with synthetic DNA duplexes using spectroscopic analysis. UV-Visible spectroscopic analysis revealed the non-intercalative binding mode. Fourier Transform Infrared spectroscopy (FTIR) analysis expose chemical shift indicated by various vibrational stretches and an increase in the intensity of base stacking was observed by Circular Dichroism (CD), respectively. This inference was further confirmed through nuclear staining technique and also in electrophoretic technique; the dye quenches the fluorescent intensity of ethidium bromide. The result of fluorescence spectroscopy was in concordance with the electrophoretic technique. In addition, the spectroscopic results were in accordance with the molecular docking studies of specific catechin compound from the catechu dye with CT-DNA. This kind of site specificity is a gain in the medicinal field as the drug can be DNA targeted for cancer therapeutics. The present work reveals that catechu dye has a noteworthy application in the field of medical bioscience. © 2016 © 2016 Taylor &amp; Francis Group, LLC.

Nucleosides, Nucleotides and Nucleic Acids

Interaction of Catechu Dye with DNA: Spectroscopic and In Silico Approach

The interaction of food colorant norbixin with calf thymus DNA (CTDNA) was investigated through UV-Visible spectroscopy, Fourier Transform Infrared (FTIR), Circular Dichroism (CD), Nuclear Magnetic Resonance (NMR), DNA melting studies, electrophoretic analysis, histological staining technique and molecular docking studies. The results indicated that norbixin interacted with CTDNA by partial intercalation mode. The binding constant (K) of norbixin with CTDNA was calculated to be 5.08 × 105 Mol-1 L. FTIR and CD studies were coupled with 1H NMR spectra revealed that norbixin intercalates partially and binds to the groove's, phosphate group, deoxyribose sugar of DNA and also induces conformational transition of B-form to A-form DNA. Agarose gel electrophoretic and histological staining technique results further prove that, norbixin specifically binds to the DNA in the cell. Moreover, molecular docking studies on the specific binding of norbixin with CTDNA have exhibited lowest conformation energy score of -3.2. Therefore, this food colorant has the ability to interact with DNA and it could emerge as a promising class of natural DNA targeted therapeutic. © 2015 Elsevier B.V. All rights reserved.

Journal	Data powered by TypesetApplied Biochemistry and Biotechnology
Publisher	Data powered by TypesetSpringer Science and Business Media LLC
ISSN	0273-2289
Open Access	0