Groove binding mediated structural modulation and DNA cleavage by quinoline appended chalcone derivative

Kumar, H.M. Suresh; Devaraji, Vinod; Prasath, R.; Jadhao, Manojkumar; Joshi, Ritika; Bhavana, P.; Ghosh, Sujit Kumar

doi:10.1016/j.saa.2015.07.010

Cited by 17 publications

(8 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To warrant the possibility of future bioactivity of any emerging drug molecule, molecular docking exercise is becoming an important approach to elucidate the interaction and binding phenomena between potential ligand and its respective macromolecular target. , The molecular docking studies of CBIQD with DNA is accomplished by the Glide docking protocol of Schrödinger suite, and the binding interaction pattern is compared with a typical intercalator Ellipticine, which is chosen for its GC specificity. It is reported that naphthalimide derivatives show higher sequence specificity toward GC base pairs. − Hence from the several ligand–DNA complexes deposited in the Protein Data Bank, one structure with PDB ID 1Z3F is selected.…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Proticity Inclined Conformational Modulation in a Highly Fluorescent Bichromophoric Naphthalimide Derivative: Hint Directed from RICT Perspective

et al. 2016

Self Cite

View full text Add to dashboard Cite

The present study embodies design, in silico DNA interaction, synthesis of benzothiazole containing naphthalimide derivative, 2-(6-chlorobenzo[d]thiazol-2-yl)-1H-benzo[de] isoquinoline-1,3(2H)-dione (CBIQD) along with its systematic photophysics, solvatochromic behavior, and solvation dynamics using an experimental and theoretical spectroscopic approach. Steady-state dual emission and biexponential fluorescence decay reveals the formation of two different excited species. Ground- and excited-state optimized geometry and the potential-energy curve obtained from DFT and TD-DFT calculation ascertained the existence of nonplanar and planar conformation. When the solvent polarity is changed from nonpolar to protic polar, the feebly emissive emission band highly intensifies probably due to the reversal of n, π*-π, π* emissive state along with consequent modulation of their energy gap that is induced by H-bonding. Excluding nonpolar solvents, in all other solvents, the Stokes shift correlates linearly with orientation polarizability, whereas in water, the story remains intriguing. With photoexcitation, intermolecular H-bonding stimulates the pyramidalization tendency of imide "N" with subsequent conformational change of GS nonplanar geometry to a coplanar one through acceptor rehybridization generating a rehybridized intramolecular charge transfer (RICT) state that caused a dramatic fluorescence upsurge. This allosteric modulation is promoted by excited-state H-bonding dynamics especially in strong H-bond donor water. A close interplay between preferential solvation and the proximity effect is evident in the emission behavior in a benzene (Bn)-ethanol (EtOH) binary mixture. Molecular docking analysis delineates considerable noncovalent sandwiched π-π stacking interactions of CBIQD with the pyrimidine rings as well as with imidazole rings of dG 6 and dG 2 base pairs of B-DNA double helix, which probably suffices the design strategy adopted. Overall, a strategic design to synthesize a highly fluorescent and potential bioactive agent is executed to revolutionize the fluorophore field due its enormous progressive importance in biochemical applications.

show abstract

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Proticity Inclined Conformational Modulation in a Highly Fluorescent Bichromophoric Naphthalimide Derivative: Hint Directed from RICT Perspective

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…To extend the research scope and collect more information about anticancer function–structure relationship, here we wish to report the photocytoxicity on tumor cells of two new gallium corrole complexes, 10‐(4‐Methoxycarbonylphenyl)‐5,15‐bis(pentafluorophenyl)corrolatogallium(III) ( 1 ‐Ga) and 5,15‐bis(4‐Methoxycarbonylphenyl)‐10‐(pentafluorophenyl)corrolatogallium(III) ( 2 ‐Ga) (scheme ). It is well known that many anticancer drugs and chemotherapeutic agents are designed to target DNA . Corroles and their complexes are proved good DNA binder and excellent artificial photonuclease .…”

Section: Methodsmentioning

confidence: 99%

Methyl Benzoate Gallium(III) corrole complexes: DNA‐binding, Photocleavage Activity, Cytotoxicity on Tumor Cells

Wang

Yuan

et al. 2016

Applied Organom Chemis

View full text Add to dashboard Cite

Two new gallium corrole complexes, 10‐(4‐Methoxycarbonylphenyl) ‐5, 15‐bis(pentafluorophenyl)corrolatogallium(III)(1‐Ga) and 5,15‐bis(4‐Methoxycarbonylphenyl)‐10‐(pentafluorophenyl)corrolatogallium(III)(2‐Ga), were synthesized and characterized. The interaction of these gallium corrole complexes with CT‐DNA was studied by fluorescence methods, UV–visible, viscosity measurements, molecular docking as well as agarose gel electrophoresis. The results revealed that both 1‐Ga and 2‐Ga interact with DNA via major groove binding and could cleavage the supercoiled plasmid DNA efficiently under irradiation. The inhibitor and singlet oxygen test indicated that singlet oxygen was the reactive oxygen species involved in the photocleavage DNA initiated by 1‐Ga or 2‐Ga. Cell viability experiments indicated that 1‐Ga and 2‐Ga show high photocytotoxicity and low dark toxicity towards tested QGY‐7701 and MHCC‐H/L tumor cell lines. Fluorescence probe tests showed the absorbed 1‐Ga and 2‐Ga in tumor cells are mainly localized in mitochondria, and the mitochondria membrane potential disruption was observed after irradiation.

show abstract

“…It is relevant to mention here that ADMQ undergoes a structural change (Scheme 1) from its native form (Form I) to β-hydroxyketo form (Form III) in physiological condition 29,33 Scheme1.Structural change of ADMQ in different environments 29 Hence the molecular docking studies has been carried out with β-hydroxy form of ADMQ to assess its preferred orientation and detailed mechanism of the interaction in the chosen binding site of ACE using Glide programme [Glide, version 6.3, Schrödinger, LLC, NY, 2014] which is used in structure based drug designing, to predict the binding affinity and to optimize small molecules as drug candidates, where flexible ligand is docked to a rigid receptor binding pocket. 34 The probe ADMQ is docked in the same active site of ACE which is preferred by captopril, to identify the molecular interaction of the probe with the binding site of the enzyme.…”

Section: Molecular Dockingmentioning

confidence: 99%

Antihypertensive activity of a quinoline appended chalcone derivative and its site specific binding interaction with a relevant target carrier protein

et al. 2015

Self Cite

View full text Add to dashboard Cite

The usefulness of heterocyclic chalcone derivative as a therapeutic target in controlling hypertension and its site specific binding interaction with model transport protein to get a clear picture about its delivery mechanism. AbstractInhibition of Angiotensin Converting Enzyme (ACE) is identified as a main therapeutic target in controlling hypertension. The principal intent of this work is to investigate the ACE inhibitory property of a quinoline appended chalcone derivative (E)-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ), and its binding mechanism with model transport protein BSA by employing steady state and time resolved fluorescence, Circular Dichroism (CD), in silico Molecular Docking, Induced Fit Docking (IFD) and Molecular Dynamics (MD) simulation. Incubation of ADMQ with kidney cortex plasma membrane shows considerable antihypertensive effect by the inhibition of ACE. ADMQ undergoes strong interaction with ACE both in absence and presence of BSA. Comparable ACE inhibitory mechanistic profile of ADMQ with standard drug captopril has been identified in terms of ligand interaction pattern, changes in secondary structural elements and protein RMSF. The steady state emission of BSA undergoes a remarkable decrement via ground state complex formation upon addition of ADMQ in aqueous buffer solution of BSA at physiological pH 7.4 contrary to the time resolved and FRET measurement where both the static andenergy transfer mechanism co-exists. Rotationally restricted ADMQ molecule shows strong binding affinity towards subdomain IIA of site I with a close proximity (2.45 nm) of the Trp 213 residue. The minor decrease of α-helical content as calculated from CD spectral measurement and 1-3 Å change in protein RMSD during MD simulation clearly indicate that the polypeptide chain is partially destabilized due to the above site specific accommodation of the host (ADMQ). A slight diminution in the ACE inhibitory profile is observed in presence of BSA; however BSA shows lesser binding towards ADMQ in presence of the target enzyme. The spectroscopic research described herein may provide enormous important information for ACE inhibition of chalcone derivative and its detail binding interaction with carrier protein for the chalcone based drug designing in medicinal chemistry research.

show abstract

Groove binding mediated structural modulation and DNA cleavage by quinoline appended chalcone derivative

Cited by 17 publications

References 69 publications

Design, Synthesis, and Proticity Inclined Conformational Modulation in a Highly Fluorescent Bichromophoric Naphthalimide Derivative: Hint Directed from RICT Perspective

Design, Synthesis, and Proticity Inclined Conformational Modulation in a Highly Fluorescent Bichromophoric Naphthalimide Derivative: Hint Directed from RICT Perspective

Methyl Benzoate Gallium(III) corrole complexes: DNA‐binding, Photocleavage Activity, Cytotoxicity on Tumor Cells

Antihypertensive activity of a quinoline appended chalcone derivative and its site specific binding interaction with a relevant target carrier protein

Contact Info

Product

Resources

About