Unleashing the binding interaction of chrysin-Cu(II) complex with the biomacromolecular targets: further studies of cell cytotoxicity and radical scavenging properties.

Flavonoids are significant dietary components and have ability to coordinate with metal ions to produce novel drug discovery leads that are superior to those of the parent flavonoids. Here, in this report, we have synthesized chrysin-Cu(II) complex (as per reported article) and characterized it further with different analytical techniques. The synthesized complex was evaluated for radical scavenging and cell cytotoxicity studies where it exhibited enhanced activity as compared to bare chrysin. The interaction studies of the complex with ct-DNA (Kb ⁓ 105 M-1), human serum albumin (HSA) and ovalbumin (Kb ⁓ 104 M-1) were evaluated using multi-spectroscopic and molecular docking studies. Groove binding mode with ct-DNA was observed as confirmed from competitive displacement studies, viscosity measurement, melting temperature estimation and docking analyses. The complex exhibited comparatively higher affinity towards ct-DNA which indicated it efficient transportation by the carrier proteins and controlled release in the target DNA.Communicated by Ramaswamy H. Sarma.

Deciphering the interactions of phytochemicals with ovalbumin, the major food allergen from egg white: spectroscopic and computational studies.

Ovalbumin (OVA), the major component of egg white, has been used as a model carrier protein to study the interaction of four bioactive phytochemicals 6-hydroxyflavone, chrysin, naringin, and naringenin. A static quenching mechanism was primarily associated with the complexation of the flavonoids with OVA. Hydrophobic forces play a major part in the stability of the complexes. The structural changes within the protein in response to flavonoid binding revealed a decrease in OVA's α-helical content. The hypothesized binding site for flavonoids in OVA overlaps with one or more immunoglobulin E-binding epitopes that may have some effect in the immunoglobulin E response pathway. The flavonoids remain in the same binding site throughout the simulation time and impart protein stability by forming different noncovalent interactions. This study presents comprehensive information about the interaction of the flavonoids with OVA and the associated structural variations after the binding, which might help researchers better comprehend similar medication pharmacodynamics and provide critical information for future therapeutic development.

Mitigation of ribose and glyoxal induced glycation, AGEs formation and aggregation of human serum albumin by citrus fruit phytochemicals naringin and naringenin: An insight into their mechanism of action.

Human serum albumin (HSA) being the most prevalent protein in the plasma is extremely vulnerable to glycation. Two flavonoids naringin and naringenin were tested for their effects on the glyoxal and ribose-induced glycation, advanced glycation end products (AGEs) and fibril formation of HSA. The inhibition of the formation of AGEs in the presence of both flavonoids demonstrated their antiglycating properties. The presence of fibrillar aggregates in the glyoxal and ribose modified HSA were also decreased by naringin and naringenin. The explanation for naringenin's stronger antiglycating potential than naringin was further investigated by examining their interactions with HSA. H-bonding and other non-covalent interactions with flavonoids stabilize HSA. Interactions of lysine and arginine residues with flavonoids may prevent the residues from getting modified during glycation process. Naringenin bind to both subdomains IIA and IIIA of HSA, protecting more residues than naringin, which only binds to subdomain IIA, may describe the higher inhibitory activity of naringenin.

Multispectroscopic studies on the molecular interactions between bovine γ-globulin and borohydride-capped silver nanoparticles.

Interactions between bovine γ-globulin (BGG) and borohydride-capped silver nanoparticles (BAgNPs) were studied using dynamic light scattering (DLS) and spectroscopic techniques such as UV-vis spectroscopy, fluorescence, and circular dichroism. The results were compared with earlier reported interactions between γ-globulin and citrate-coated AgNPs (CAgNPs). BAgNPs were synthesized and characterized. Irrespective of the coating on AgNPs, nanoparticles had formed ground-state complexes with the protein. CAgNPs, as well as BAgNPs had caused static quenching of tryptophan (Trp) fluorescence of the protein. The change in the capping agent from citrate to borohydride weakened the binding of nanoparticles with the protein. But the same change in capping agent had increased the fluorescence quenching efficiency of AgNPs. Hydrogen bonding and van der Waals interactions were involved in BGG-BAgNPs complex similar to the CAgNPs complex with γ-globulin. Polarity of the Trp microenvironment in BGG was not altered using BAgNPs as opposed to CAgNPs, as supported using synchronous and three-dimensional fluorescence. Resonance light scattering experiments also suggested nano-bio conjugation. Far-UV and near-UV circular dichroism (CD) spectra respectively pointed towards changes in the secondary and tertiary structure of BGG by BAgNPs, which was not observed for CAgNPs.

A review on prevention of glycation of proteins: Potential therapeutic substances to mitigate the severity of diabetes complications.

Non-enzymatic reaction involving carbonyl of reducing sugars and amino groups in proteins produces advanced glycation end products (AGEs). AGE accumulation in vivo is a crucial factor in the progression of metabolic and pathophysiological mechanisms like obesity, diabetes, coronary artery disease, neurological disorders, and chronic renal failure. The body's own defense mechanism, synthetic inhibitors, and natural inhibitors can all help to prevent the glycation of proteins. Synthetic inhibitors have the potential to suppress the glycation of proteins through a variety of pathways. They could avoid Amadori product development by tampering with the addition of sugars to the proteins. Besides which, the free radical scavenging and blocking crosslink formation could be another mechanism behind their anti-glycation properties. In comparison with synthetic substances, naturally occurring plant products have been found to be comparatively non-toxic, cheap, and usable in an ingestible form. This review gives a brief introduction of the Maillard reaction; formation, characterization and pathology related to AGEs, potential therapeutic approaches against glycation, natural and synthetic inhibitors of glycation and their probable mechanism of action. The scientific community could get benefit from the combined knowledge about important molecules, which will further guide to the design and development of new pharmaceutical compounds.

Elucidation of molecular interactions between human γD-crystallin and quercetin, an inhibitor against tryptophan oxidation.

Different post-translational changes in eye lens crystallin proteins contribute towards the development of cataract. We have studied in vitro oxidative modification of tryptophan (Trp) residues of human γD-crystallin (HGD) towards formation of N-formylkynurenine (NFK) associated with cataractogenesis. This oxidation was found to be inhibited by quercetin at relatively low concentration. Interactions between quercetin and HGD were further studied using fluorescence techniques. Binding and quenching constants were determined as ∼104 M-1. Static quenching of fluorescence due to HGD-quercetin complex formation at ground state was confirmed by finding excited state life time of Trp residues. Energy transfer occurred between the protein and quercetin. Hydrogen bonding and/or van der Waals interactions were involved between HGD and quercetin. Synchronous and three-dimensional fluorescence along with far-UV CD studies suggested no major conformational alterations occurred in HGD due to quercetin binding. Experimental observations were supported by the docking results.Communicated by Ramaswamy H. Sarma.

An investigation into the identification of potential inhibitors of SARS-CoV-2 main protease using molecular docking study.

A new strain of a novel infectious disease affecting millions of people, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been declared as a pandemic by the World Health Organization (WHO). Currently, several clinical trials are underway to identify specific drugs for the treatment of this novel virus. The inhibition of the SARS-CoV-2 main protease is necessary for the blockage of the viral replication. Here, in this study, we have utilized a blind molecular docking approach to identify the possible inhibitors of the SARS-CoV-2 main protease, by screening a total of 33 molecules which includes natural products, anti-virals, anti-fungals, anti-nematodes and anti-protozoals. All the studied molecules could bind to the active site of the SARS-CoV-2 protease (PDB: 6Y84), out of which rutin (a natural compound) has the highest inhibitor efficiency among the 33 molecules studied, followed by ritonavir (control drug), emetine (anti-protozoal), hesperidin (a natural compound), lopinavir (control drug) and indinavir (anti-viral drug). All the molecules, studied out here could bind near the crucial catalytic residues, HIS41 and CYS145 of the main protease, and the molecules were surrounded by other active site residues like MET49, GLY143, HIS163, HIS164, GLU166, PRO168, and GLN189. As this study is based on molecular docking, hence being particular about the results obtained, requires extensive wet-lab experimentation and clinical trials under in vitro as well as in vivo conditions.Communicated by Ramaswamy H. Sarma.

Non-enzymatic glycation of human serum albumin modulates its binding efficacy towards bioactive flavonoid chrysin: A detailed study using multi-spectroscopic and computational methods.

The non-enzymatic glycation of plasma proteins by reducing sugars have important consequences on the conformational and functional properties of protein. The formation of advanced glycation end products (AGEs) is responsible for cell death and other pathological conditions. We have synthesized the glycated human serum albumin (gHSA) and characterized the same by using differential spectroscopic measurements. The aim of the present study is to determine the effect of glycation on the binding of human serum albumin (HSA) with bioactive flavonoid chrysin, which possesses anti-cancer, anti-inflammatory and anti-oxidant activities. The interaction of chrysin with HSA and gHSA was studied using multi-spectroscopic, molecular docking and molecular dynamics (MD) simulation techniques. Chrysin quenched the intrinsic fluorescence of both HSA and gHSA by static quenching mechanism. The value of the binding constant (Kb) for the interaction of HSA-chrysin complex (4.779 ± 0.623 × 105 M-1 at 300 K) was found to be higher than that of gHSA-chrysin complex (2.206 ± 0.234 × 105 M-1 at 300 K). Hence, non-enzymatic glycation of HSA significantly reduced its binding affinity towards chrysin. The % α-helicity of HSA was found to get enhanced upon binding with chrysin, and minimal changes were observed for the gHSA-chrysin complex. Site marker probe studies indicated that chrysin binds to subdomain IIA and IIIA of both HSA and gHSA. The results from molecular docking and MD simulation studies correlated well with the experimental findings. Electrostatic interactions followed by hydrogen bonding and hydrophobic interactions played major roles in the binding process. These observations may have some useful insights into the field of pharmaceutics.

Protective actions of bioactive flavonoids chrysin and luteolin on the glyoxal induced formation of advanced glycation end products and aggregation of human serum albumin: In vitro and molecular docking analysis.

The post-translational modification of proteins by nonenzymatic glycation (NEG) and the accumulation of AGEs are the two underlying factors associated with the long-term pathogenesis in diabetes. Glyoxal (GO) is a reactive intermediate which has the ability to modify proteins and generate AGEs at a faster rate. Human serum albumin (HSA) being the most abundant serum protein has a higher chance to be modified by NEG. The key objective of the present study is to investigate the potency of chrysin and luteolin as antiglycating and antifibrillating agents in the GO-mediated glycation and fibril formation of HSA. AGEs formation were confirmed from the absorption and fluorescence spectral measurements. Both the flavonoids were able to quench the AGEs fluorescence intensity in vitro indicating the antiglycating nature of the molecules. The formation of fibrils in the GO-modified HSA was confirmed by the Thioflavin T (ThT) fluorescence assay and the flavonoids were found to exihibit the antifibrillation properties in vitro. Docking results suggested that both the flavonoids interact with various amino acid residues of subdomain IIA including glycation prone lysines and arginines via non-covalent forces and further stabilized the structure of HSA, which further explains their mechanisms of action as antiglycating and antifibrillating agents.

Exploring the interaction of bioactive kaempferol with serum albumin, lysozyme and hemoglobin: A biophysical investigation using multi-spectroscopic, docking and molecular dynamics simulation studies.

In recent years research based on kaempferol (KMP) has shown its potential therapeutic applications in medicinal chemistry and clinical biology. Therefore, to understand its molecular recognition mechanism, we studied its interactions with the carrier proteins, namely, human serum albumin (HSA), bovine hemoglobin (BHb) and hen egg white lysozyme (HEWL). The ligand, KMP was able to quench the intrinsic fluorescence of these three proteins efficiently through static quenching mode. The binding constant (Kb) for the interactions of KMP with these three proteins were found in the following order: HSA-KMP > BHb-KMP > HEWL-KMP. Different non-covalent forces such as hydrogen bonding and hydrophobic forces played a major role in the binding of KMP with HSA and HEWL, whereas hydrogen bonding and van der Waals forces contribute to the complexation of BHb with KMP. KMP was able to alter the micro-environment near the Trp fluorophore of the proteins. KMP altered the secondary structural component of all three proteins. The putative binding sites and the residues surrounding the KMP molecule within the respective protein matrix were determined through molecular docking and molecular dynamics (MD) simulation studies. The conformational flexibility of the ligand KMP and the three individual proteins were also evident from the MD simulation studies.