An \u3cem\u3ein-vitro\u3c/em\u3e Elucidation of Inhibitory Potential of Carminic Acid: Possible Therapeutic Approach for Neurodegenerative Diseases

Protein misfolding leads to several human pathologies. So far, there has not been much success on the remediations of these protein conformational disorders. Since these diseases arise as a result of protein aggregation, hence inhibition of aggregation could be a promising approach for designing new therapeutics. For which; polyphenols, antibiotics and other small compounds have been tested by the researchers in the recent past, but so far there has not been much success. Here we have investigated the effect of carminic acid over Human serum albumin in an in vitro manner. It was observed that there was severe resistance in the increment of fluorescence intensity in the presence of carminic acid when observed through ANS, ThT and RLS, which was further supported by CD and Congo red assay. Microscopic analysis also confirmed that there was aggregation inhibition in the presence of180μM carminic acid. ROS and SDS-PAGE results also established the same. Furthermore, molecular docking was performed to understand the interacting residues which were found to be Arg, Leu, Glu. It is noteworthy that inhibitory effect was concentration dependent and maximum inhibition was found to be in presence of 180 μM of carminic acid. These results shall be helpful in designing the new therapeutics against amyloidosis

A multitechnique approach to probe the interaction of a therapeutic tyrosine kinase inhibitor nintedanib and bovine serum albumin

<p>Drug and protein interaction provides a structural guideline in the rational drug designing and in the synthesis of new and improved drugs with greater efficacy. We have examined here the interaction tendency and mechanism of nintedanib (NTB), an anticancer drug (tyrosine kinase inhibitor) with bovine serum albumin (BSA), by spectroscopic techniques. The decline in Stern–Volmer quenching constants and binding constant with the temperature rise suggests that BSA forms a complex with NTB. Binding constant obtained by modified Stern–Volmer equation at 3 temperatures was realized to be of the order of ~10⁴ M⁻¹. Negative Δ<i>G</i> (~−5.93 kcal mol⁻¹), Δ<i>H</i> (−3.74 kcal mol⁻¹), and Δ<i>S</i> (−1.50 kcal mol⁻¹) values exhibited a spontaneous and exothermic reaction between BSA and NTB. NTB molecule interacts with BSA by forming hydrogen bonds, as elucidated by fluorescence results. Moreover, a minor increment in the helical conformation of BSA upon its binding to NTB was observed by circular dichroism spectroscopy. The modification in protein’s symmetry and a decline in hydrodynamic radii were observed in the presence of NTB (from ~3.6 to ~3 nm) as obtained by the dynamic light scattering measurement results.</p

Correction: A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins.

[This corrects the article DOI: 10.1371/journal.pone.0158833.]

A Multiparametric Analysis of the Synergistic Impact of Anti-Parkinson\u27s Drugs on the Fibrillation of Human Serum Albumin

Protein aggregation have been associated with several human neurodegenerative diseases, such as Parkinson\u27s and Alzheimer\u27s diseases. There are several small molecules that can reduce aggregation of proteins. The present study aimed to test the hypothesis that the application of more than one inhibitor either simultaneously or consecutively may result in more efficient inhibition of protein aggregation. To this end, the anti-amyloidogenic behaviour of benserazide hydrochloride (BH) and levodopa (LD) individually and in combination (BH + LD) was investigated using various biophysical, microscopic, and computational techniques. BH, LD, and BH + LD treatments showed inhibitory effects on protein aggregation and had the ability to minimise the amyloid-induced cytotoxicity in human neuroblastoma cell line (SH-SY5Y). The two drugs in combination showed synergism (combination index, CI \u3c 1) between them. These drugs also destabilised the preformed fibrils of human serum albumin (HSA). Our studies consistently showed that the BH + LD treatment showed highest efficacy towards inhibition and disaggregation of amyloid fibrils in comparison to treatment with BH and LD individually. Therefore, application of drugs in combination against fibrillogenesis may represent a new route for development of means for prevention or delaying of the aggregation-related diseases

Binding of anti-cardiovascular drug to serum albumin: an insight in the light of spectroscopic and computational approaches

<p>Isoprenaline hydrochloride is a potential cardiovascular drug helps in the smooth functioning of the heart muscles. So, we have performed the binding study of ISO with BSA. This study was investigated by UV absorption, fluorescence, synchronous fluorescence, circular dichroism, etc. The analysis of intrinsic fluorescence data showed the low binding affinity of ISO. The binding constant <i>K</i>_<i>b</i> was 2.8 × 103 M-1 and binding stoichiometry (n) was approximately one and the Gibb’s free energy change at 310 K was determined to be -8.69 kcal mol⁻¹. Negative Gibb’s free energy change shows the spontaneity of the BSA and ISO interaction. We have found ISO-induced alternation in the UV absorption, synchronous fluorescence and CD spectra in the absence and presence of the quencher indicates the complex formation. In synchronous fluorescence, red shift was obtained because of the complex formation of BSA and ISO. The distance (<i>r</i>) between the BSA (donor) and ISO (acceptor) was 2.89 nm, determined by FRET. DLS measurements interpreted complex formation due to the reduction in hydrodynamic radii of the protein in the presence of the drug. The binding site of ISO was found to be nearer to Trp 134 with the help of molecular docking and the Δ<i>G</i>° was found to be –10.2 kcal mol⁻¹. The esterase activity result suggests that ISO acts as competitive inhibitor. Thus, this study would help to determine the binding capacity of the drug to the protein which may indicate the efficiency of diffusion of ISO into the blood for the treatment of heart diseases.</p

A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins - Fig 5

<p>Absorption spectra of HSA (A) and BSA (B) gradually titrated with NDGA upto 1:10 molar ratio of albumins to NDGA, at 37°C.</p

FRET parameters obtained from NDGA binding to HSA and BSA.

<p>FRET parameters obtained from NDGA binding to HSA and BSA.</p