Inhibition of transcription factor assembly and structural stability on mitoxantrone binding with DNA

Khan, Shah Per N.; Danishuddin, Mohd; Khan, Asad

doi:10.1042/bsr20090083

Cited by 14 publications

(3 citation statements)

References 28 publications

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“…When ligand molecules bind independently to a set of equivalent sites on a macromolecule, the equilibrium between free and bound molecules is given by the equation [25,26]:…”

Section: Binding Equilibriummentioning

confidence: 99%

Mitoxantrone Induced Impediment of Histone Acetylation and Structural Flexibility of the Protein

Khan

Yennamalli

Subbarao

et al. 2010

Cell Biochem Biophys

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Mitoxantrone (MTX), a choice of drug in cancer chemotherapeutic regime, is a potent and less toxic among anthracycline class of drugs. Here, we study the molecular interaction of MTX, with histone and its acetylation dynamics. Its binding with histone core protein was predicted with CD and UV-visible spectroscopic techniques. The MTX-protein complex resulted in the impediment of the histone acetyltransferase (HAT) activity in a dose dependent manner on MTX binding. Interestingly, the concentration dependent reduction in acetylated state of specific lysines K9/K14 was also observed on MTX treatment in vivo. The molecular distance r, between donor (histone H3) and acceptor (MTX) was estimated using Förster's theory of non-radiation energy transfer and the detailed binding phenomenon was expounded. MTX binding site near N-terminal lysines is characterized with an association constant of the order of 10(4). The positive thermodynamic values of both ∆H° and ∆S° were suggestive that the hydrophobic interactions dominate in MTX-protein binding. The binding site allocation predicted by computational modeling placed the drug molecule near N-terminal lysine K9 and K14 of histone H3, and corroborate with the thermodynamic interaction model. The study establishes that MTX-histone interaction affects protein acetylation state and also provided a mechanistic model for its binding. Hence, MTX interaction may affect chromatin structure and implicates its role in transcriptional regulation at epigenetic level.

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“…When ligand molecules bind independently to a set of equivalent sites on a macromolecule, the equilibrium between free and bound molecules is given by the equation [25,26]:…”

Section: Binding Equilibriummentioning

confidence: 99%

Mitoxantrone Induced Impediment of Histone Acetylation and Structural Flexibility of the Protein

Khan

Yennamalli

Subbarao

et al. 2010

Cell Biochem Biophys

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“…Positive values of both ΔS and ΔH are typical for hydrophobic interaction, while negative values of both can be regarded as indicating van der Waals forces and hydrogen bonds. However, positive values of ΔH and negative values of ΔS describe electrostatic interaction between ionic species in an aqueous solution 79 , 80 . Hence, the obtained results indicate that binding between the studied 7-MEOTA-THA thio-/ureas 12 – 22 and ctDNA was spontaneous due to negative ΔG values at all three temperatures, and the positive values of ΔH and ΔS showed that hydrophobic interactions play a central role in the binding of the studied 7-MEOTA-THA thio-/ureas 12 – 22 with ctDNA.…”

Section: Resultsmentioning

confidence: 99%

In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers

Janočková

Korábečný

Plsikova

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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A combination of biochemical, biophysical and biological techniques was used to study calf thymus DNA interaction with newly synthesized 7-MEOTA-tacrine thiourea 12 – 17 and urea heterodimers 18 – 22 , and to measure interference with type I and II topoisomerases. Their biological profile was also inspected in vitro on the HL-60 cell line using different flow cytometric techniques (cell cycle distribution, detection of mitochondrial membrane potential dissipation, and analysis of metabolic activity/viability). The compounds exhibited a profound inhibitory effect on topoisomerase activity (e.g. compound 22 inhibited type I topoisomerase at 1 µM concentration). The treatment of HL-60 cells with the studied compounds showed inhibition of cell growth especially with hybrids containing thiourea ( 14–17 ) and urea moieties ( 21 and 22 ). Moreover, treatment of human dermal fibroblasts with the studied compounds did not indicate significant cytotoxicity. The observed results suggest beneficial selectivity of the heterodimers as potential drugs to target cancer cells.

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“…The negative value of Gibbs energy indicates that the binding process is spontaneous in nature. Moreover, the negative values of both entropy change and enthalpy change indicate that van der Waals interactions and hydrogen bonds are predominant forces involved in the formation pioglitazone‐DNA complex …”

Section: Resultsmentioning

confidence: 99%

Study on the interaction of antidiabetic drug Pioglitazone with calf thymus DNA using spectroscopic techniques

Qumaizi

Anwer

Ahmad

et al. 2018

J of Molecular Recognition

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Pioglitazone is an antidiabetic drug used to treat type 2 diabetes mellitus. Interaction of Pioglitazone with calf thymus DNA was investigated using multispectroscopic techniques and molecular docking study. Quenching and binding constant was calculated at 3 different temperatures. The binding constant of Pioglitazone with calf thymus DNA was calculated to be 6.49 × 10 M at 293 K. The quenching mechanism was found to be a static process, and thermodynamic parameters revealed van der Waals interactions and hydrogen bonds to be the major force working in Pioglitazone-DNA interaction. Pioglitazone follows the nonintercalative mode of binding and was involved in complex formation with DNA through minor groove binding and electrostatic interactions. Experiments like KI quenching studies, dye displacement assays, Circular Dichroism (CD) spectroscopy, DNA melting study, and viscosity measurements studies supported the nonintercalative mode of binding. This was further corroborated by molecular docking studies.

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Inhibition of transcription factor assembly and structural stability on mitoxantrone binding with DNA

Cited by 14 publications

References 28 publications

Mitoxantrone Induced Impediment of Histone Acetylation and Structural Flexibility of the Protein

Mitoxantrone Induced Impediment of Histone Acetylation and Structural Flexibility of the Protein

In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers

Study on the interaction of antidiabetic drug Pioglitazone with calf thymus DNA using spectroscopic techniques

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