The Experts below are selected from a list of 468 Experts worldwide ranked by ideXlab platform

Shweta Agarwal - One of the best experts on this subject based on the ideXlab platform.

  • Investigation of Anti-Cancer Drug Nimustine Interaction with Calf Thymus DNA
    MAPAN, 2016
    Co-Authors: Deepti Chadha, Shweta Agarwal, Ranjana Mehrotra
    Abstract:

    Nimustine, a chloroethyl Nitrosourea Derivative (CENU), is an antineoplastic agent, which is used for the treatment of various types of cancer. The present study focuses on the prediction and investigation of binding properties of nimustine with DNA using molecular modeling and UV–Visible spectroscopic technique. The docking study show that nimustine plausibly binds within the major groove of DNA. Further analysis of docking suggests direct interaction of nimustine with the moieties of heterocyclic nitrogenous bases of DNA. The free binding energy value of the best nimustine-DNA docked conformer is predicted as −4.31 kcal/mol using docking results.The molecular modeling study also reveals that the interaction between nimustine and DNA is majorly governed by van der Waals forces, hydrogen bonding and hydrophobic interactions, whereas the contribution of electrostatic forces stands negligible. Further, UV–Visible spectra of free calf thymus DNA and its complexes with varying concentration of nimustine indicate the binding constant ( K _ a ) value as 3.27 × 10^3 M^−1, which suggests moderate interaction of nimustine with DNA. The spectroscopic results are further used to calculate the binding free energy of the complex using the relation Δ G = − RT ln ( K _ a ). This accounts for a value of −4.79 kcal/mol. It corroborates well with the docking outcomes. The results of present study may help in designing and synthesis of new chloroethyl Nitrosourea Derivatives with improved efficacy and specificity for the target molecules.

  • Investigation of Anti-Cancer Drug Nimustine Interaction with Calf Thymus DNA
    MAPAN, 2016
    Co-Authors: Deepti Chadha, Shweta Agarwal, Ranjana Mehrotra
    Abstract:

    Nimustine, a chloroethyl Nitrosourea Derivative (CENU), is an antineoplastic agent, which is used for the treatment of various types of cancer. The present study focuses on the prediction and investigation of binding properties of nimustine with DNA using molecular modeling and UV–Visible spectroscopic technique. The docking study show that nimustine plausibly binds within the major groove of DNA. Further analysis of docking suggests direct interaction of nimustine with the moieties of heterocyclic nitrogenous bases of DNA. The free binding energy value of the best nimustine-DNA docked conformer is predicted as −4.31 kcal/mol using docking results.The molecular modeling study also reveals that the interaction between nimustine and DNA is majorly governed by van der Waals forces, hydrogen bonding and hydrophobic interactions, whereas the contribution of electrostatic forces stands negligible. Further, UV–Visible spectra of free calf thymus DNA and its complexes with varying concentration of nimustine indicate the binding constant ( K _ a ) value as 3.27 × 10^3 M^−1, which suggests moderate interaction of nimustine with DNA. The spectroscopic results are further used to calculate the binding free energy of the complex using the relation Δ G = − RT ln ( K _ a ). This accounts for a value of −4.79 kcal/mol. It corroborates well with the docking outcomes. The results of present study may help in designing and synthesis of new chloroethyl Nitrosourea Derivatives with improved efficacy and specificity for the target molecules.

  • A Structural Insight into Major Groove Directed Binding of Nitrosourea Derivative Nimustine with DNA: A Spectroscopic Study
    2016
    Co-Authors: Shweta Agarwal, Deepak Kuma Jangi, Ranjana Mehrotra, Neelam Lohani, M. R. Rajeswari
    Abstract:

    Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl Nitrosourea Derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon nimustine-DNA interaction. Thermodynamic parameters of nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of nimustine with nitrogenous bases guanine (C6 =O6) and thymine (C4 =O4) in DNA major groove. CD spectra of nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug’s action at molecular level. Results, demonstrated here, may contribute in the development of new nitrosoure

  • A structural insight into major groove directed binding of Nitrosourea Derivative nimustine with DNA: a spectroscopic study.
    PLoS ONE, 2014
    Co-Authors: Shweta Agarwal, Ranjana Mehrotra, Neelam Lohani, Deepak Kumar Jangir, M. R. Rajeswari
    Abstract:

    Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl Nitrosourea Derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon nimustine-DNA interaction. Thermodynamic parameters of nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of nimustine with nitrogenous bases guanine (C6 = O6) and thymine (C4 = O4) in DNA major groove. CD spectra of nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug's action at molecular level. Results, demonstrated here, may contribute in the development of new Nitrosourea therapeutics with better efficacy and fewer side effects. Times Cited: 4 (fro

  • FTIR spectra of free DNA and nimustine-DNA complexes.
    2014
    Co-Authors: Shweta Agarwal, Ranjana Mehrotra, Neelam Lohani, Deepak Kumar Jangir, M. R. Rajeswari
    Abstract:

    FTIR spectra of free calf thymus DNA and its complexes with Nitrosourea Derivative nimustine at different molar ratios were collected in the region of 1800 cm−1 to 700 cm cm−1.

Ranjana Mehrotra - One of the best experts on this subject based on the ideXlab platform.

  • Investigation of Anti-Cancer Drug Nimustine Interaction with Calf Thymus DNA
    MAPAN, 2016
    Co-Authors: Deepti Chadha, Shweta Agarwal, Ranjana Mehrotra
    Abstract:

    Nimustine, a chloroethyl Nitrosourea Derivative (CENU), is an antineoplastic agent, which is used for the treatment of various types of cancer. The present study focuses on the prediction and investigation of binding properties of nimustine with DNA using molecular modeling and UV–Visible spectroscopic technique. The docking study show that nimustine plausibly binds within the major groove of DNA. Further analysis of docking suggests direct interaction of nimustine with the moieties of heterocyclic nitrogenous bases of DNA. The free binding energy value of the best nimustine-DNA docked conformer is predicted as −4.31 kcal/mol using docking results.The molecular modeling study also reveals that the interaction between nimustine and DNA is majorly governed by van der Waals forces, hydrogen bonding and hydrophobic interactions, whereas the contribution of electrostatic forces stands negligible. Further, UV–Visible spectra of free calf thymus DNA and its complexes with varying concentration of nimustine indicate the binding constant ( K _ a ) value as 3.27 × 10^3 M^−1, which suggests moderate interaction of nimustine with DNA. The spectroscopic results are further used to calculate the binding free energy of the complex using the relation Δ G = − RT ln ( K _ a ). This accounts for a value of −4.79 kcal/mol. It corroborates well with the docking outcomes. The results of present study may help in designing and synthesis of new chloroethyl Nitrosourea Derivatives with improved efficacy and specificity for the target molecules.

  • Investigation of Anti-Cancer Drug Nimustine Interaction with Calf Thymus DNA
    MAPAN, 2016
    Co-Authors: Deepti Chadha, Shweta Agarwal, Ranjana Mehrotra
    Abstract:

    Nimustine, a chloroethyl Nitrosourea Derivative (CENU), is an antineoplastic agent, which is used for the treatment of various types of cancer. The present study focuses on the prediction and investigation of binding properties of nimustine with DNA using molecular modeling and UV–Visible spectroscopic technique. The docking study show that nimustine plausibly binds within the major groove of DNA. Further analysis of docking suggests direct interaction of nimustine with the moieties of heterocyclic nitrogenous bases of DNA. The free binding energy value of the best nimustine-DNA docked conformer is predicted as −4.31 kcal/mol using docking results.The molecular modeling study also reveals that the interaction between nimustine and DNA is majorly governed by van der Waals forces, hydrogen bonding and hydrophobic interactions, whereas the contribution of electrostatic forces stands negligible. Further, UV–Visible spectra of free calf thymus DNA and its complexes with varying concentration of nimustine indicate the binding constant ( K _ a ) value as 3.27 × 10^3 M^−1, which suggests moderate interaction of nimustine with DNA. The spectroscopic results are further used to calculate the binding free energy of the complex using the relation Δ G = − RT ln ( K _ a ). This accounts for a value of −4.79 kcal/mol. It corroborates well with the docking outcomes. The results of present study may help in designing and synthesis of new chloroethyl Nitrosourea Derivatives with improved efficacy and specificity for the target molecules.

  • A Structural Insight into Major Groove Directed Binding of Nitrosourea Derivative Nimustine with DNA: A Spectroscopic Study
    2016
    Co-Authors: Shweta Agarwal, Deepak Kuma Jangi, Ranjana Mehrotra, Neelam Lohani, M. R. Rajeswari
    Abstract:

    Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl Nitrosourea Derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon nimustine-DNA interaction. Thermodynamic parameters of nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of nimustine with nitrogenous bases guanine (C6 =O6) and thymine (C4 =O4) in DNA major groove. CD spectra of nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug’s action at molecular level. Results, demonstrated here, may contribute in the development of new nitrosoure

  • A structural insight into major groove directed binding of Nitrosourea Derivative nimustine with DNA: a spectroscopic study.
    PLoS ONE, 2014
    Co-Authors: Shweta Agarwal, Ranjana Mehrotra, Neelam Lohani, Deepak Kumar Jangir, M. R. Rajeswari
    Abstract:

    Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl Nitrosourea Derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon nimustine-DNA interaction. Thermodynamic parameters of nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of nimustine with nitrogenous bases guanine (C6 = O6) and thymine (C4 = O4) in DNA major groove. CD spectra of nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug's action at molecular level. Results, demonstrated here, may contribute in the development of new Nitrosourea therapeutics with better efficacy and fewer side effects. Times Cited: 4 (fro

  • FTIR spectra of free DNA and nimustine-DNA complexes.
    2014
    Co-Authors: Shweta Agarwal, Ranjana Mehrotra, Neelam Lohani, Deepak Kumar Jangir, M. R. Rajeswari
    Abstract:

    FTIR spectra of free calf thymus DNA and its complexes with Nitrosourea Derivative nimustine at different molar ratios were collected in the region of 1800 cm−1 to 700 cm cm−1.

M. R. Rajeswari - One of the best experts on this subject based on the ideXlab platform.

  • A Structural Insight into Major Groove Directed Binding of Nitrosourea Derivative Nimustine with DNA: A Spectroscopic Study
    2016
    Co-Authors: Shweta Agarwal, Deepak Kuma Jangi, Ranjana Mehrotra, Neelam Lohani, M. R. Rajeswari
    Abstract:

    Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl Nitrosourea Derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon nimustine-DNA interaction. Thermodynamic parameters of nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of nimustine with nitrogenous bases guanine (C6 =O6) and thymine (C4 =O4) in DNA major groove. CD spectra of nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug’s action at molecular level. Results, demonstrated here, may contribute in the development of new nitrosoure

  • A structural insight into major groove directed binding of Nitrosourea Derivative nimustine with DNA: a spectroscopic study.
    PLoS ONE, 2014
    Co-Authors: Shweta Agarwal, Ranjana Mehrotra, Neelam Lohani, Deepak Kumar Jangir, M. R. Rajeswari
    Abstract:

    Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl Nitrosourea Derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon nimustine-DNA interaction. Thermodynamic parameters of nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of nimustine with nitrogenous bases guanine (C6 = O6) and thymine (C4 = O4) in DNA major groove. CD spectra of nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug's action at molecular level. Results, demonstrated here, may contribute in the development of new Nitrosourea therapeutics with better efficacy and fewer side effects. Times Cited: 4 (fro

  • A structural insight into major groove directed binding of Nitrosourea Derivative nimustine with DNA: a spectroscopic study.
    Public Library of Science (PLoS), 1
    Co-Authors: Shweta Agarwal, Ranjana Mehrotra, Neelam Lohani, Deepak Kumar Jangir, M. R. Rajeswari
    Abstract:

    Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl Nitrosourea Derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon nimustine-DNA interaction. Thermodynamic parameters of nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of nimustine with nitrogenous bases guanine (C6 = O6) and thymine (C4 = O4) in DNA major groove. CD spectra of nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug's action at molecular level. Results, demonstrated here, may contribute in the development of new Nitrosourea therapeutics with better efficacy and fewer side effects

Neelam Lohani - One of the best experts on this subject based on the ideXlab platform.

  • A Structural Insight into Major Groove Directed Binding of Nitrosourea Derivative Nimustine with DNA: A Spectroscopic Study
    2016
    Co-Authors: Shweta Agarwal, Deepak Kuma Jangi, Ranjana Mehrotra, Neelam Lohani, M. R. Rajeswari
    Abstract:

    Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl Nitrosourea Derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon nimustine-DNA interaction. Thermodynamic parameters of nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of nimustine with nitrogenous bases guanine (C6 =O6) and thymine (C4 =O4) in DNA major groove. CD spectra of nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug’s action at molecular level. Results, demonstrated here, may contribute in the development of new nitrosoure

  • A structural insight into major groove directed binding of Nitrosourea Derivative nimustine with DNA: a spectroscopic study.
    PLoS ONE, 2014
    Co-Authors: Shweta Agarwal, Ranjana Mehrotra, Neelam Lohani, Deepak Kumar Jangir, M. R. Rajeswari
    Abstract:

    Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl Nitrosourea Derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon nimustine-DNA interaction. Thermodynamic parameters of nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of nimustine with nitrogenous bases guanine (C6 = O6) and thymine (C4 = O4) in DNA major groove. CD spectra of nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug's action at molecular level. Results, demonstrated here, may contribute in the development of new Nitrosourea therapeutics with better efficacy and fewer side effects. Times Cited: 4 (fro

  • FTIR spectra of free DNA and nimustine-DNA complexes.
    2014
    Co-Authors: Shweta Agarwal, Ranjana Mehrotra, Neelam Lohani, Deepak Kumar Jangir, M. R. Rajeswari
    Abstract:

    FTIR spectra of free calf thymus DNA and its complexes with Nitrosourea Derivative nimustine at different molar ratios were collected in the region of 1800 cm−1 to 700 cm cm−1.

  • A structural insight into major groove directed binding of Nitrosourea Derivative nimustine with DNA: a spectroscopic study.
    Public Library of Science (PLoS), 1
    Co-Authors: Shweta Agarwal, Ranjana Mehrotra, Neelam Lohani, Deepak Kumar Jangir, M. R. Rajeswari
    Abstract:

    Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl Nitrosourea Derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon nimustine-DNA interaction. Thermodynamic parameters of nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of nimustine with nitrogenous bases guanine (C6 = O6) and thymine (C4 = O4) in DNA major groove. CD spectra of nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug's action at molecular level. Results, demonstrated here, may contribute in the development of new Nitrosourea therapeutics with better efficacy and fewer side effects

J. Vignoud - One of the best experts on this subject based on the ideXlab platform.

  • Hepatic intra-arterial infusion of fotemustine: pharmacokinetics
    Cancer Chemotherapy and Pharmacology, 1992
    Co-Authors: R. Fety, C. Lucas, P. Solere, V. Cour, J. Vignoud
    Abstract:

    Fotemustine is a new Nitrosourea Derivative that contains an alpha-aminophosphonic acid and has a short half-life and a high plasma clearance. As myelosuppression occurs as the dose-limiting toxicity, local drug delivery has been investigated in the treatment of liver metastases arising from colorectal cancer. A pharmacokinetic study was undertaken in patients who received either i. v. or hepatic intra-arterial (HIA) infusion of 100 mg/m^2 fotemustine so as to estimate the advantage of local chemotherapy, considering the pharmacokinetic differences between the two routes together with the resultant toxicities (when available). Our findings substantiated the hypothesis that a 4-h HIA infusion of fotemustine would result in a lower exposure of healthy tissues to the drug, since the AUC measured in systemic plasma was reduced by approximately 50% following such treatment as compared with i. v. infusion. This reduction in AUC should indicate a manyfold increase in exposure of the liver tumour to the alkylating properties of the drug, since it represents the proportion of the dose that has degraded within the liver. The first-pass liver-extraction ratio of fotemustine given as a 4-h HIA infusion, which ranged from 0.4 to 0.9 as estimated in patients receiving i. v. and HIA infusions in a cross-over study, argues for further investigation of HIA fotemustine infusion for the treatment of liver metastases so as to increase the response rate and decrease the occurrence of major toxic side effects in such patients.