Stabilization of a potential anticancer thiosemicarbazone derivative in Sudlow site I of human serum albumin: In vitro spectroscopy coupled with molecular dynamics simulation

Ganorkar, Kapil; Mukherjee, Soham; Singh, P.; Ghosh, Sujit Kumar

doi:10.1016/j.bpc.2020.106509

Cited by 9 publications

(5 citation statements)

References 74 publications

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“…Any ligand that binds to protein may induce structural and conformational changes in the macromolecule, which is very important for the pharmacokinetics and pharmacodynamics [ 45 ]. MD can be used to study the stability and kinetic characteristics of astilbin–HSA complexes [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

Molecular Insight into the Binding of Astilbin with Human Serum Albumin and Its Effect on Antioxidant Characteristics of Astilbin

et al. 2022

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Astilbin is a dihydroflavonol glycoside identified in many natural plants and functional food with promising biological activities which is used as an antioxidant in the pharmaceutical and food fields. This work investigated the interaction between astilbin and human serum albumin (HSA) and their effects on the antioxidant activity of astilbin by multi-spectroscopic and molecular modeling studies. The experimental results show that astilbin quenches the fluorescence emission of HSA through a static quenching mechanism. Astilbin and HSA prefer to bind at the Site Ⅰ position, which is mainly maintained by electrostatic force, hydrophobic and hydrogen bonding interactions. Multi-spectroscopic and MD results indicate that the secondary structure of HSA could be changed because of the interaction of astilbin with HSA. DPPH radical scavenging assay shows that the presence of HSA reduces the antioxidant capacity of astilbin. The explication of astilbin–HSA binding mechanism will provide insights into clinical use and resource development of astilbin in food and pharmaceutical industries.

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Section: Resultsmentioning

confidence: 99%

Molecular Insight into the Binding of Astilbin with Human Serum Albumin and Its Effect on Antioxidant Characteristics of Astilbin

et al. 2022

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“…Felix GX software is used for fluorescence data collection and analysis. The fluorescence lifetime decay curves obtained are fitted with mono-, bi-, and triexponential functions using the following equation F ( t ) = prefix∑ i α i exp false( prefix− τ / τ i false) where α i is a pre-exponential factor representing the fractional contribution to the time-resolved decay of the component with a lifetime τ i .…”

Section: Experimental Methodsmentioning

confidence: 99%

“…The Schrödinger suite of Maestro was employed for in silico molecular docking analysis. The crystal structures of DAHTS and DNA (PDB ID 1Z3F) were prepared in LigPrep (ligand preparation) and Protein Preparation Wizard, respectively . The main moto behind docking is to generate active binding sites that could form a stable DNA–ligand complex.…”

Section: Experimental Methodsmentioning

confidence: 99%

“…16 Felix GX software is used for fluorescence data collection and analysis. The fluorescence lifetime decay curves obtained are fitted with mono-, bi-, and triexponential functions using the following equation 43…”

Section: Time-resolved Fluorescencementioning

confidence: 99%

“…The crystal structures of DAHTS and DNA (PDB ID 1Z3F) were prepared in LigPrep (ligand preparation) and Protein Preparation Wizard, respectively. 43 The main moto behind docking is to generate active binding sites that could form a stable DNA−ligand complex. The XP (extra precision) Glide mode was used for specific binding of DAHTS with DNA.…”

Section: In Silico Molecular Docking Analysismentioning

confidence: 99%

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Switching of the Polarity-Sensitive Aggregation Pattern of a Thiosemicarbazone-Based Anticancer Luminophore and Its Involvement in Cellular Apoptosis of the Human Lung Cancer Cell Line

et al. 2023

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Elucidation of the photophysical and biochemical properties of small molecules can facilitate their applications as prospective therapeutic imaging (theragnostic) agents. Herein, we demonstrate the luminescence behavior of a strategically designed potential therapeutic thiosemicarbazone derivative, (E)-1-(4-(diethylamino)-2-hydroxybenzylidene)-4,4-dimethylthiosemicarbazide (DAHTS), accompanied by the illustration of its solvation and solvation dynamics using spectroscopic techniques and exploring its promising antitumor activities by adopting the necessary biochemical assays. Solvent-dependent photophysical properties, namely UV−vis absorption, fluorescence emission, and excitation profiles, concentrationdependent studies, and time-resolved fluorescence decays, serve as footprints to explain the existence of DAHTS monomers, its excitedstate intramolecular proton transfer (ESIPT) product, and dimeric and aggregated forms. The emission intensity progressively intensifies with increasing polarity and proticity of the solvents up to MeOH, but in water, a sudden dip is seen. Solvent polarity and H-bonding modulate the fluorescence behavior of the primary emission peak and significantly influence the formation of the dimer and DAHTS aggregates. The designed luminophore (DAHTS) exhibits significant antiproliferative activity against the human lung cancer (A549) cell lines with inhibitory concentrations (IC 50 ) of 16.88 and 11.92 μM for 24 and 48 h, respectively. DAHTS effectively reduces the cell viability and induces cytotoxicity with extensive morphological changes in A549 cells in the form of spikes when compared to the normal HEK cell lines. More importantly, it increases the p53 expression at the mRNA level that consolidates its potential therapeutic activity. The effect of DAHTS on apoptotic pathways against the A549 cell line has been investigated to determine its probable mechanism of cell death. Thus, the all-inclusive understanding of the photophysical properties and the necessary biochemical assays put forward important steps toward tailoring the thiosemicarbazone core structure for favorable cancer theragnostic applications in academic and pharmaceutical research.

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Synthesis and characterization of the new ligand, 1,2,4-triazino[5,6-b]indol-3-ylimino methyl naphthalene-2-ol and its Ni(II) and Cu(II) complexes: comparative studies of their in vitro DNA and HSA Binding

2022

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Stabilization of a potential anticancer thiosemicarbazone derivative in Sudlow site I of human serum albumin: In vitro spectroscopy coupled with molecular dynamics simulation

Cited by 9 publications

References 74 publications

Molecular Insight into the Binding of Astilbin with Human Serum Albumin and Its Effect on Antioxidant Characteristics of Astilbin

Molecular Insight into the Binding of Astilbin with Human Serum Albumin and Its Effect on Antioxidant Characteristics of Astilbin

Switching of the Polarity-Sensitive Aggregation Pattern of a Thiosemicarbazone-Based Anticancer Luminophore and Its Involvement in Cellular Apoptosis of the Human Lung Cancer Cell Line

Synthesis and characterization of the new ligand, 1,2,4-triazino[5,6-b]indol-3-ylimino methyl naphthalene-2-ol and its Ni(II) and Cu(II) complexes: comparative studies of their in vitro DNA and HSA Binding

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