Exploring the interactions of therapeutic phytochemicals, flavokawain b, pinostrobin and 6-shogaol with human serum albumin: Spectroscopic and molecular docking investigations / Shevin Rizal Feroz

The rhizomes of the plants of Zingiberaceae family are rich sources of bioactive phytochemicals and therefore, are major targets for discovering new phytomedicines. Three of these phytochemicals, namely, flavokawain B (FB), pinostrobin (PS) and 6-shogaol (6S) have shown various therapeutic properties including antioxidant, anticarcinogenic, anti-inflammatory and antimicrobial activities. The interactions of these compounds with the main in vivo drug carrier, human serum albumin (HSA) were investigated using a multitude of spectroscopic methods, supported by molecular docking studies. Significant quenching of HSA fluorescence intensity was observed upon titration of the protein with these compounds. Analysis of the fluorescence data revealed the involvement of static quenching phenomena in these interactions, thus suggesting the formation of ligand–HSA complexes. The association constants, Ka of these ligand–HSA systems were found to lie in the range, 0.63–1.03 × 105 M−1 at 25 °C, characteristic of moderate affinity binding. Thermodynamic analysis of the binding data showed that the binding reactions were accompanied by negative enthalpy (−ΔH) and positive entropy (+ΔS) changes, which were indicative of the involvement of hydrophobic and van der Waals forces along with hydrogen bonds in the complex formation. This was corroborated by molecular docking results depicting the formation of hydrogen bonds and identification of hydrophobic residues in the vicinity of the docked ligands. Synchronous and three-dimensional fluorescence data suggested significant change in the microenvironment around Tyr and Trp residues of HSA upon binding to these compounds. Far-UV circular dichroism results indicated relatively higher thermal stability of the protein in the presence of these ligands. Competitive drug displacement experiments along with docking simulation results suggested a clear binding preference of FB and PS for Sudlow’s site I (subdomain IIA) of HSA, while 6S was able to bind favourably to Sudlow’s site I as well as with Sudlow’s site II (subdomain IIIA)

Characteristics and thermodynamics of the interaction of 6-shogaol with human serum albumin as studied by isothermal titration calorimetry

The interaction between 6-shogaol, a pharmacologically active ginger constituent, and human serum albumin (HSA), the main in vivo drug transporter, was investigated using isothermal titration calorimetry (ITC). The value of the binding constant, Ka (5.02 ± 1.37 × 104 M−1) obtained for the 6-shogaol-HSA system suggested intermediate affinity. Analysis of the ITC data revealed feasibility of the binding reaction due to favorable enthalpy and entropy changes. The values of the thermodynamic parameters suggested involvement of van der Waals forces, hydrogen bonds and hydrophobic interactions in the 6-shogaol-HSA complex formation

Characteristics and thermodynamics of the interaction of 6-shogaol with human serum albumin as studied by isothermal titration calorimetry

ABSTRACT The interaction between 6-shogaol, a pharmacologically active ginger constituent, and human serum albumin (HSA), the main in vivo drug transporter, was investigated using isothermal titration calorimetry (ITC). The value of the binding constant, Ka (5.02 ± 1.37 × 104 M−1) obtained for the 6-shogaol-HSA system suggested intermediate affinity. Analysis of the ITC data revealed feasibility of the binding reaction due to favorable enthalpy and entropy changes. The values of the thermodynamic parameters suggested involvement of van der Waals forces, hydrogen bonds and hydrophobic interactions in the 6-shogaol-HSA complex formation

Characteristics and thermodynamics of the interaction of 6-shogaol with human serum albumin as studied by isothermal titration calorimetry

ABSTRACT The interaction between 6-shogaol, a pharmacologically active ginger constituent, and human serum albumin (HSA), the main in vivo drug transporter, was investigated using isothermal titration calorimetry (ITC). The value of the binding constant, Ka (5.02 ± 1.37 × 104 M−1) obtained for the 6-shogaol-HSA system suggested intermediate affinity. Analysis of the ITC data revealed feasibility of the binding reaction due to favorable enthalpy and entropy changes. The values of the thermodynamic parameters suggested involvement of van der Waals forces, hydrogen bonds and hydrophobic interactions in the 6-shogaol-HSA complex formation

Biochemical and structural characterization of a novel cold-active esterase-like protein from the psychrophilic yeast Glaciozyma antarctica

Dienelactone hydrolase, an α/β hydrolase enzyme, catalyzes the hydrolysis of dienelactone to maleylacetate, an intermediate for the Krebs cycle. Genome sequencing of the psychrophilic yeast, Glaciozyma antarctica predicted a putative open reading frame (ORF) for dienelactone hydrolase (GaDlh) with 52% sequence similarity to that from Coniophora puteana. Phylogenetic tree analysis showed that GaDlh is closely related to other reported dienelactone hydrolases, and distantly related to other α/β hydrolases. Structural prediction using MODELLER 9.14 showed that GaDlh has the same α/β hydrolase fold as other dienelactone hydrolases and esterase/lipase enzymes, with a catalytic triad consisting of Cys–His–Asp and a G–x–C–x–G–G motif. Based on the predicted structure, GaDlh exhibits several characteristics of cold-adapted proteins such as glycine clustering in the binding pocket, reduced protein core hydrophobicity, and the absence of proline residues in loops. The putative ORF was amplified, cloned, and overexpressed in an Escherichia coli expression system. The recombinant protein was overexpressed as soluble proteins and was purified via Ni–NTA affinity chromatography. Biochemical characterization of GaDlh revealed that it has an optimal temperature at 10 °C and that it retained almost 90% of its residual activity when incubated for 90 min at 10 °C. The optimal pH was at pH 8.0 and it was stable between pH 5–9 when incubated for 60 min (more than 50% residual activity). Its Km value was 256 μM and its catalytic efficiency was 81.7 s−1. To our knowledge, this is the first report describing a novel cold-active dienelactone hydrolase-like protein

Curcumin and Its Derivatives as Potential Antimalarial and Anti-Inflammatory Agents: A Review on Structure–Activity Relationship and Mechanism of Action

Curcumin, one of the major ingredients of turmeric (Curcuma longa), has been widely reported for its diverse bioactivities, including against malaria and inflammatory-related diseases. However, curcumin’s low bioavailability limits its potential as an antimalarial and anti-inflammatory agent. Therefore, research on the design and synthesis of novel curcumin derivatives is being actively pursued to improve the pharmacokinetic profile and efficacy of curcumin. This review discusses the antimalarial and anti-inflammatory activities and the structure–activity relationship (SAR), as well as the mechanisms of action of curcumin and its derivatives in malarial treatment. This review provides information on the identification of the methoxy phenyl group responsible for the antimalarial activity and the potential sites and functional groups of curcumin for structural modification to improve its antimalarial and anti-inflammatory actions, as well as potential molecular targets of curcumin derivatives in the context of malaria and inflammation

Spectrofluorometric and Molecular Docking Studies on the Binding of Curcumenol and Curcumenone to Human Serum Albumin

Curcumenol and curcumenone are two major constituents of the plants of medicinally important genus of Curcuma, and often govern the pharmacological effect of these plant extracts. These two compounds, isolated from C. zedoaria rhizomes were studied for their binding to human serum albumin (HSA) using the fluorescence quench titration method. Molecular docking was also performed to get a more detailed insight into their interaction with HSA at the binding site. Additions of these sesquiterpenes to HSA produced significant fluorescence quenching and blue shifts in the emission spectra of HSA. Analysis of the fluorescence data pointed toward moderate binding affinity between the ligands and HSA, with curcumenone showing a relatively higher binding constant (2.46 × 105 M−1) in comparison to curcumenol (1.97 × 104 M−1). Cluster analyses revealed that site I is the preferred binding site for both molecules with a minimum binding energy of −6.77 kcal·mol−1. However, binding of these two molecules to site II cannot be ruled out as the binding energies were found to be −5.72 and −5.74 kcal·mol−1 for curcumenol and curcumenone, respectively. The interactions of both ligands with HSA involved hydrophobic interactions as well as hydrogen bonding