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Loic Toupet - One of the best experts on this subject based on the ideXlab platform.

  • crystal structure determination spectroscopic characterization and biological profile of a tailored ionic Molecular Entity sn iv iminodiacetic acid piperazinediium conjugate in vitro dna rna binding studies topo i inhibition activity cytotoxic and sy
    RSC Advances, 2015
    Co-Authors: Farukh Arjmand, Imtiyaz Yousuf, Yusra Zaidi, Loic Toupet
    Abstract:

    A novel ionic tin(IV) iminodiacetic acid–piperazinediium conjugate (1) was designed and synthesized as a potential antitumor chemotherapeutic Molecular Entity and was thoroughly characterized by elemental analysis, FT-IR, 1H, 13C and 119Sn NMR, ESI MS and single crystal X-ray crystallography. Complex 1 resulted from the proton transfer reaction between iminodiacetic acid (H2IDA) and piperazine (pipz), and its subsequent complexation with tin(IV) chloride salt. 1 crystallized in orthorhombic space group Ima2 and comprises of an anionic metallic unit, a piperazinediium cation and a chloride ion. In continuity of our previous strategy in search of robust metal-based antitumor drug entities exhibiting reduced systemic toxicity, we have carried out in vitro interaction studies of 1 with ct-DNA, tRNA and Topo I targets, to validate its chemotherapeutic potential. Complex 1 exhibited more avid binding propensity with RNA which was reflected by its higher Kb and K values with RNA as compared to DNA. Topoisomerase inhibition activity of 1 was performed by gel electrophoresis which revealed significant inhibitory effect on the catalytic activity of the enzyme at 30 μM concentration. Molecular docking studies of the complex were carried out with DNA (PDB ID: 1BNA), RNA (PDB ID: 6TNA) and Topo I (PDB ID: ISC7) targets to ascertain the specific binding mode thereby substantiated the spectroscopic results. Cytotoxic studies were carried out on a panel of eight human cancer cell lines; U373MG, PC3, Hop62, HL60, HCT15, SK-OV-3, HeLa and MCF-7 by SRB assay which revealed significant regression specifically for HCT15, HOP62, MCF-7 and SK-OV-3 human cancer cell lines (GI50 value < 10) as compared to the standard drug Adriamycin. Systemic toxicity of 1 was carried out by the estimation of oxidative stress biomarkers such as lipid peroxides (expressed as malondialdehyde; MDA) and reduced glutathione (GSH) levels in kidney and liver homogenates and the study was supported by the histopathologic examination of kidney and liver of female Wistar rats.

  • design and synthesis of new zn ii nalidixic acid dach based topo ii inhibiting Molecular Entity chemotherapeutic potential validated by its in vitro binding profile pbr322 cleavage activity and Molecular docking studies with dna and rna Molecular tar
    Inorganica Chimica Acta, 2014
    Co-Authors: Farukh Arjmand, Imtiyaz Yousuf, Mohd Afzal, Loic Toupet
    Abstract:

    Abstract Nalidixic acid–DACH based Zn(II) Molecular Entity (1) was synthesized and thoroughly characterized by spectroscopic techniques (FT-IR, 1H and 13C NMR, ESI-MS) and single crystal X-ray crystallography as a potential chemotherapeutic drug candidate. The comparative in vitro binding studies of complex 1 with targets like CT-DNA and yeast tRNA were carried out by employing UV–Vis, emission spectroscopy, circular dichroism and viscosity which revealed higher binding affinity of 1 towards yeast tRNA as compared to CT-DNA. Complex 1 cleaves pBR322 plasmid via hydrolytic pathway (validated by T4 religation assay); in addition, 1 also exhibited significant inhibitory effects on the catalytic activity of Topo-II at a concentration of 30 μM. Further, validation of the interaction studies was accomplished by carrying out Molecular docking studies with DNA, RNA and Topo-II targets. This work also advances our knowledge for the development and design of small RNA targeted therapeutic molecules which were relatively under exploited drug targets.

  • Design and synthesis of new Zn(II) nalidixic acid–DACH based Topo-II inhibiting Molecular Entity: Chemotherapeutic potential validated by its in vitro binding profile, pBR322 cleavage activity and Molecular docking studies with DNA and RNA Molecular
    Inorganica Chimica Acta, 2014
    Co-Authors: Farukh Arjmand, Imtiyaz Yousuf, Mohd Afzal, Loic Toupet
    Abstract:

    Abstract Nalidixic acid–DACH based Zn(II) Molecular Entity (1) was synthesized and thoroughly characterized by spectroscopic techniques (FT-IR, 1H and 13C NMR, ESI-MS) and single crystal X-ray crystallography as a potential chemotherapeutic drug candidate. The comparative in vitro binding studies of complex 1 with targets like CT-DNA and yeast tRNA were carried out by employing UV–Vis, emission spectroscopy, circular dichroism and viscosity which revealed higher binding affinity of 1 towards yeast tRNA as compared to CT-DNA. Complex 1 cleaves pBR322 plasmid via hydrolytic pathway (validated by T4 religation assay); in addition, 1 also exhibited significant inhibitory effects on the catalytic activity of Topo-II at a concentration of 30 μM. Further, validation of the interaction studies was accomplished by carrying out Molecular docking studies with DNA, RNA and Topo-II targets. This work also advances our knowledge for the development and design of small RNA targeted therapeutic molecules which were relatively under exploited drug targets.

Farukh Arjmand - One of the best experts on this subject based on the ideXlab platform.

  • a multifunctional Molecular Entity cuii sniv heterobimetallic complex as a potential cancer chemotherapeutic agent dna binding cleavage sod mimetic topoisomerase iα inhibitory and in vitro cytotoxic activities
    RSC Advances, 2015
    Co-Authors: Sartaj Tabassum, Farukh Arjmand, Ahmad Asim, Rais Ahmad Khan, Dhivya Rajakumar, Perumalsamy Balaji, Mohammad Abdulkader Akbarsha
    Abstract:

    New chiral L-valine-derived Schiff base complexes with the bioactive heterocyclic ligand scaffold pyrazole (Hpz) were designed and synthesized with a view to find their potential as anticancer chemotherapeutic drug candidates. The monometallic chemical entities CuII (1) and ZnII (2), and heterobimetallic CuII–SnIV (3), and ZnII–SnIV (4) were synthesized and characterized adopting various spectroscopic (UV-vis, IR, 1H 13C and 119Sn NMR, EPR and ESI-MS) and analytical methods. In vitro, CT-DNA-binding profiles of 1–4 were studied by UV-vis, fluorescence spectroscopy, and circular dichroism. The results display the significantly higher binding affinity of heterobimetallic complexes 3 and 4 than monometallic complexes 1 and 2. This could be attributed to the dual binding mode facilitating a preferential electrostatic interaction via SnIV towards the surface phosphate oxygen of the sugar–phosphate backbone of the DNA double helix, in addition to the covalent overlap of CuII to N7 of the guanine of the DNA. Moreover, complex 3 exhibited significantly efficient DNA cleavage activity involving the formation of the superoxide radical as well as the hydroxyl radical as the reactive species. The SOD-like activity of 3 and 4 was evaluated using a xanthine/xanthine oxidase assay, which showed SOD activity in the micromolar range for both the heterobimetallic complexes viz., (IC50) 0.082 μM for 3 and 12 μM for 4. Furthermore, 3 showed high inhibitory activity against Topo-Iα at a concentration of 20 μM as IC50, suggesting that complex 3 is an efficient DNA cleaving agent. In vitro studies on the anticancer activity against the HepG2 hepatocellular carcinoma cell line revealed that both complexes 3 and 4 have the capability to kill the chosen cancer cell, but the efficiency of complex 3 is 10 times higher than 4. The mode of cell death induced by complex 3 is primarily apoptosis as revealed by AO/EB staining, Hoechst 33258 staining, and assessment of the mitochondrial trans-membrane potential.

  • crystal structure determination spectroscopic characterization and biological profile of a tailored ionic Molecular Entity sn iv iminodiacetic acid piperazinediium conjugate in vitro dna rna binding studies topo i inhibition activity cytotoxic and sy
    RSC Advances, 2015
    Co-Authors: Farukh Arjmand, Imtiyaz Yousuf, Yusra Zaidi, Loic Toupet
    Abstract:

    A novel ionic tin(IV) iminodiacetic acid–piperazinediium conjugate (1) was designed and synthesized as a potential antitumor chemotherapeutic Molecular Entity and was thoroughly characterized by elemental analysis, FT-IR, 1H, 13C and 119Sn NMR, ESI MS and single crystal X-ray crystallography. Complex 1 resulted from the proton transfer reaction between iminodiacetic acid (H2IDA) and piperazine (pipz), and its subsequent complexation with tin(IV) chloride salt. 1 crystallized in orthorhombic space group Ima2 and comprises of an anionic metallic unit, a piperazinediium cation and a chloride ion. In continuity of our previous strategy in search of robust metal-based antitumor drug entities exhibiting reduced systemic toxicity, we have carried out in vitro interaction studies of 1 with ct-DNA, tRNA and Topo I targets, to validate its chemotherapeutic potential. Complex 1 exhibited more avid binding propensity with RNA which was reflected by its higher Kb and K values with RNA as compared to DNA. Topoisomerase inhibition activity of 1 was performed by gel electrophoresis which revealed significant inhibitory effect on the catalytic activity of the enzyme at 30 μM concentration. Molecular docking studies of the complex were carried out with DNA (PDB ID: 1BNA), RNA (PDB ID: 6TNA) and Topo I (PDB ID: ISC7) targets to ascertain the specific binding mode thereby substantiated the spectroscopic results. Cytotoxic studies were carried out on a panel of eight human cancer cell lines; U373MG, PC3, Hop62, HL60, HCT15, SK-OV-3, HeLa and MCF-7 by SRB assay which revealed significant regression specifically for HCT15, HOP62, MCF-7 and SK-OV-3 human cancer cell lines (GI50 value < 10) as compared to the standard drug Adriamycin. Systemic toxicity of 1 was carried out by the estimation of oxidative stress biomarkers such as lipid peroxides (expressed as malondialdehyde; MDA) and reduced glutathione (GSH) levels in kidney and liver homogenates and the study was supported by the histopathologic examination of kidney and liver of female Wistar rats.

  • design and synthesis of new zn ii nalidixic acid dach based topo ii inhibiting Molecular Entity chemotherapeutic potential validated by its in vitro binding profile pbr322 cleavage activity and Molecular docking studies with dna and rna Molecular tar
    Inorganica Chimica Acta, 2014
    Co-Authors: Farukh Arjmand, Imtiyaz Yousuf, Mohd Afzal, Loic Toupet
    Abstract:

    Abstract Nalidixic acid–DACH based Zn(II) Molecular Entity (1) was synthesized and thoroughly characterized by spectroscopic techniques (FT-IR, 1H and 13C NMR, ESI-MS) and single crystal X-ray crystallography as a potential chemotherapeutic drug candidate. The comparative in vitro binding studies of complex 1 with targets like CT-DNA and yeast tRNA were carried out by employing UV–Vis, emission spectroscopy, circular dichroism and viscosity which revealed higher binding affinity of 1 towards yeast tRNA as compared to CT-DNA. Complex 1 cleaves pBR322 plasmid via hydrolytic pathway (validated by T4 religation assay); in addition, 1 also exhibited significant inhibitory effects on the catalytic activity of Topo-II at a concentration of 30 μM. Further, validation of the interaction studies was accomplished by carrying out Molecular docking studies with DNA, RNA and Topo-II targets. This work also advances our knowledge for the development and design of small RNA targeted therapeutic molecules which were relatively under exploited drug targets.

  • Design and synthesis of new Zn(II) nalidixic acid–DACH based Topo-II inhibiting Molecular Entity: Chemotherapeutic potential validated by its in vitro binding profile, pBR322 cleavage activity and Molecular docking studies with DNA and RNA Molecular
    Inorganica Chimica Acta, 2014
    Co-Authors: Farukh Arjmand, Imtiyaz Yousuf, Mohd Afzal, Loic Toupet
    Abstract:

    Abstract Nalidixic acid–DACH based Zn(II) Molecular Entity (1) was synthesized and thoroughly characterized by spectroscopic techniques (FT-IR, 1H and 13C NMR, ESI-MS) and single crystal X-ray crystallography as a potential chemotherapeutic drug candidate. The comparative in vitro binding studies of complex 1 with targets like CT-DNA and yeast tRNA were carried out by employing UV–Vis, emission spectroscopy, circular dichroism and viscosity which revealed higher binding affinity of 1 towards yeast tRNA as compared to CT-DNA. Complex 1 cleaves pBR322 plasmid via hydrolytic pathway (validated by T4 religation assay); in addition, 1 also exhibited significant inhibitory effects on the catalytic activity of Topo-II at a concentration of 30 μM. Further, validation of the interaction studies was accomplished by carrying out Molecular docking studies with DNA, RNA and Topo-II targets. This work also advances our knowledge for the development and design of small RNA targeted therapeutic molecules which were relatively under exploited drug targets.

Imtiyaz Yousuf - One of the best experts on this subject based on the ideXlab platform.

  • crystal structure determination spectroscopic characterization and biological profile of a tailored ionic Molecular Entity sn iv iminodiacetic acid piperazinediium conjugate in vitro dna rna binding studies topo i inhibition activity cytotoxic and sy
    RSC Advances, 2015
    Co-Authors: Farukh Arjmand, Imtiyaz Yousuf, Yusra Zaidi, Loic Toupet
    Abstract:

    A novel ionic tin(IV) iminodiacetic acid–piperazinediium conjugate (1) was designed and synthesized as a potential antitumor chemotherapeutic Molecular Entity and was thoroughly characterized by elemental analysis, FT-IR, 1H, 13C and 119Sn NMR, ESI MS and single crystal X-ray crystallography. Complex 1 resulted from the proton transfer reaction between iminodiacetic acid (H2IDA) and piperazine (pipz), and its subsequent complexation with tin(IV) chloride salt. 1 crystallized in orthorhombic space group Ima2 and comprises of an anionic metallic unit, a piperazinediium cation and a chloride ion. In continuity of our previous strategy in search of robust metal-based antitumor drug entities exhibiting reduced systemic toxicity, we have carried out in vitro interaction studies of 1 with ct-DNA, tRNA and Topo I targets, to validate its chemotherapeutic potential. Complex 1 exhibited more avid binding propensity with RNA which was reflected by its higher Kb and K values with RNA as compared to DNA. Topoisomerase inhibition activity of 1 was performed by gel electrophoresis which revealed significant inhibitory effect on the catalytic activity of the enzyme at 30 μM concentration. Molecular docking studies of the complex were carried out with DNA (PDB ID: 1BNA), RNA (PDB ID: 6TNA) and Topo I (PDB ID: ISC7) targets to ascertain the specific binding mode thereby substantiated the spectroscopic results. Cytotoxic studies were carried out on a panel of eight human cancer cell lines; U373MG, PC3, Hop62, HL60, HCT15, SK-OV-3, HeLa and MCF-7 by SRB assay which revealed significant regression specifically for HCT15, HOP62, MCF-7 and SK-OV-3 human cancer cell lines (GI50 value < 10) as compared to the standard drug Adriamycin. Systemic toxicity of 1 was carried out by the estimation of oxidative stress biomarkers such as lipid peroxides (expressed as malondialdehyde; MDA) and reduced glutathione (GSH) levels in kidney and liver homogenates and the study was supported by the histopathologic examination of kidney and liver of female Wistar rats.

  • design and synthesis of new zn ii nalidixic acid dach based topo ii inhibiting Molecular Entity chemotherapeutic potential validated by its in vitro binding profile pbr322 cleavage activity and Molecular docking studies with dna and rna Molecular tar
    Inorganica Chimica Acta, 2014
    Co-Authors: Farukh Arjmand, Imtiyaz Yousuf, Mohd Afzal, Loic Toupet
    Abstract:

    Abstract Nalidixic acid–DACH based Zn(II) Molecular Entity (1) was synthesized and thoroughly characterized by spectroscopic techniques (FT-IR, 1H and 13C NMR, ESI-MS) and single crystal X-ray crystallography as a potential chemotherapeutic drug candidate. The comparative in vitro binding studies of complex 1 with targets like CT-DNA and yeast tRNA were carried out by employing UV–Vis, emission spectroscopy, circular dichroism and viscosity which revealed higher binding affinity of 1 towards yeast tRNA as compared to CT-DNA. Complex 1 cleaves pBR322 plasmid via hydrolytic pathway (validated by T4 religation assay); in addition, 1 also exhibited significant inhibitory effects on the catalytic activity of Topo-II at a concentration of 30 μM. Further, validation of the interaction studies was accomplished by carrying out Molecular docking studies with DNA, RNA and Topo-II targets. This work also advances our knowledge for the development and design of small RNA targeted therapeutic molecules which were relatively under exploited drug targets.

  • Design and synthesis of new Zn(II) nalidixic acid–DACH based Topo-II inhibiting Molecular Entity: Chemotherapeutic potential validated by its in vitro binding profile, pBR322 cleavage activity and Molecular docking studies with DNA and RNA Molecular
    Inorganica Chimica Acta, 2014
    Co-Authors: Farukh Arjmand, Imtiyaz Yousuf, Mohd Afzal, Loic Toupet
    Abstract:

    Abstract Nalidixic acid–DACH based Zn(II) Molecular Entity (1) was synthesized and thoroughly characterized by spectroscopic techniques (FT-IR, 1H and 13C NMR, ESI-MS) and single crystal X-ray crystallography as a potential chemotherapeutic drug candidate. The comparative in vitro binding studies of complex 1 with targets like CT-DNA and yeast tRNA were carried out by employing UV–Vis, emission spectroscopy, circular dichroism and viscosity which revealed higher binding affinity of 1 towards yeast tRNA as compared to CT-DNA. Complex 1 cleaves pBR322 plasmid via hydrolytic pathway (validated by T4 religation assay); in addition, 1 also exhibited significant inhibitory effects on the catalytic activity of Topo-II at a concentration of 30 μM. Further, validation of the interaction studies was accomplished by carrying out Molecular docking studies with DNA, RNA and Topo-II targets. This work also advances our knowledge for the development and design of small RNA targeted therapeutic molecules which were relatively under exploited drug targets.

Imrana Naseem - One of the best experts on this subject based on the ideXlab platform.

  • probing the interaction of a coumarin di 2 picolyl amine hybrid drug like Molecular Entity with human serum albumin multiple spectroscopic and Molecular modeling techniques
    Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2019
    Co-Authors: Saman Khan, Atif Zafar, Imrana Naseem
    Abstract:

    Abstract HSA is an important plasma protein responsible for transport of drug molecules. Coumarin derivatives play critical role as anticancer, antidiabetic and antiparkinson agents. In our lab we have synthesized coumarin-based pharmacophore, di(2-picolyl)amine-3(bromoacetyl) coumarin (ligand-L) endowed with anticancer activity. Anticancer agents binding mode of HSA provides valuable pharmacological information and is a structural guidance in synthesizing new drugs with greater efficacy. Thus, binding mechanism of ligand-L with HSA was explored using spectroscopic and Molecular docking techniques. UV–Vis spectroscopy demonstrates hyperchromism in the absorbance spectra of HSA on addition of ligand-L suggesting interaction of ligand-L with HSA. Fluorescence spectroscopy indicates quenching in the fluorescence of HSA in the presence of ligand-L confirming the complex formation and this binding follows static mechanism. Steady state fluorescence spectroscopy revealed high binding affinity between ligand-L and HSA with a 1:1 stoichiometry. Thermodynamic parameters obtained by ITC suggest that the interaction between ligand-L and HSA is mainly driven by van der Waals forces and hydrogen bonds, and the negative value of ΔG is an indication of spontaneous binding process. Competitive binding and Molecular docking experiments showed that the binding site of ligand-L mainly resides in sub-domain IIA of HSA. CD experiments revealed no significant conformational changes in the secondary structure of HSA on binding of ligand-L. We also found that esterase-like activity of HSA was not affected by ligand-L. In conclusion, this study demonstrates binding mechanism of ligand-L with HSA, and the binding did not induce conformational changes in HSA. This study is likely to provide better understanding of transport and delivery of ligand-L via HSA. Overall, it will provide insights into pharmacokinetic properties of ligand-L and designing new ligand-L based derivatives with greater efficacy.

  • synthesis of novel coumarin nucleus based dpa drug like Molecular Entity in vitro dna cu ii binding dna cleavage and pro oxidant mechanism for anticancer action
    PLOS ONE, 2017
    Co-Authors: Saman Khan, Atif Zafar, Ali Mohammed Malla, Imrana Naseem
    Abstract:

    : Despite substantial research on cancer therapeutics, systemic toxicity and drug-resistance limits the clinical application of many drugs like cisplatin. Therefore, new chemotherapeutic strategies against different malignancies are needed. Targeted cancer therapy is a new paradigm for cancer therapeutics which targets pathways or chemical entities specific to cancer cells than normal ones. Unlike normal cells, cancer cells contain elevated copper which plays an integral role in angiogenesis. Copper is an important metal ion associated with chromatin DNA, particularly with guanine. Thus, targeting copper via copper-specific chelators in cancer cells can serve as an effective anticancer strategy. New pharmacophore di(2-picolyl)amine (DPA)-3(bromoacetyl) coumarin (ligand-L) was synthesized and characterized by IR, ESI-MS, 1H- and 13C-NMR. Binding ability of ligand-L to DNA/Cu(II) was evaluated using a plethora of biophysical techniques which revealed ligand-L-DNA and ligand-L-Cu(II) interaction. Competitive displacement assay and docking confirmed non-intercalative binding mode of ligand-L with ctDNA. Cyclic voltammetry confirmed ligand-L causes quasi reversible Cu(II)/Cu(I) conversion. Further, acute toxicity studies revealed no toxic effects of ligand-L on mice. To evaluate the chemotherapeutic potential and anticancer mechanism of ligand-L, DNA damage via pBR322 cleavage assay and reactive oxygen species (ROS) generation were studied. Results demonstrate that ligand-L causes DNA cleavage involving ROS generation in the presence of Cu(II). In conclusion, ligand-L causes redox cycling of Cu(II) to generate ROS which leads to oxidative DNA damage and pro-oxidant cancer cell death. These findings will establish ligand-L as a lead molecule to synthesize new molecules with better copper chelating and pro-oxidant properties against different malignancies.

Santiago Ramon Y Cajal - One of the best experts on this subject based on the ideXlab platform.