Human serum albumin directed formation of cadmium telluride quantum dots: Applications in biosensing, anti-bacterial activities and cell cytotoxicity measurements.

Although cadmium-based quantum dots (QDs) are highly promising candidates for numerous biological applications, their intrinsic toxicity limits their pertinency in living systems. Surface functionalization of QDs with appropriate molecules could reduce the toxicity level. Herein, we have synthesized the smaller sized (1-5 nm) aqueous-compatible biogenic CdTe QDs using human serum albumin (HSA) as a surface passivating agent via a greener approach. HSA-functionalized CdTe QDs have been explored in multiple in vitro sensing and biological applications, namely, (1) sensing, (2) anti-bacterial and (3) anti-cancer properties. Using CdTe-HSA QDs as a fluorescence probe, a simple fluorometric method has been developed for highly sensitive and selective detection of blood marker bilirubin and hazardous Hg2+ ion with a limit of detection (LOD) of 3.38 and 0.53 ng/mL, respectively. CdTe-HSA QDs also acts as a sensor for standard antibiotics, tetracycline and rifampicin with LOD values of 41.34 and 114.99 ng/mL, respectively. Nano-sized biogenic CdTe-HSA QDs have shown promising anti-bacterial activities against both gram-negative, E. coli and gram-positive, E. faecalis strains confirming more effectiveness against E. faecalis strains. The treatment of human cervical cancer cell lines (HeLa cells) with the synthesized QDs reflected the proficient cytotoxic properties of QDs.

Complexation of turmeric and curcumin mediated silver nanoparticles with human serum albumin: Further investigation into the protein-corona formation, anti-bacterial effects and cell cytotoxicity studies.

Biosynthesized noble metal nanoparticles have been of recent interest due to their broad implications in the future biomedicinal field. We have synthesized silver nanoparticle using turmeric-extract and its major component curcumin as reducing and stabilizing agents. Further, we have investigated the protein-NPs interaction focusing the inspection of the role of biosynthesized AgNPs on any conformational changes of the protein, binding and thermodynamic parameters using spectroscopic techniques. Fluorescence quenching studies revealed that both CUR-AgNPs and TUR-AgNPs have moderate binding affinities (∼104 M-1) towards human serum albumin (HSA) and static quenching mechanism was involved in the binding. Estimated thermodynamic parameters indicate the involvement of hydrophobic forces in the binding processes. The surface charge potential of the biosynthesized AgNPs became more negative upon complexation with HSA as observed from Zeta potential measurements. Antibacterial efficacies of the biosynthesized AgNPs were evaluated against Escherichia coli (gram-negative) and Enterococcus faecalis (gram-positive) bacterial strains. The AgNPs were found to destroy the cancer (HeLa) cell lines in vitro. The overall findings of our study successfully outline the detailed insight of the protein corona formation by biocompatible AgNPs and their biological applications concerning the future scope in the biomedicinal field.

Formation of ZnS quantum dots using green tea extract: applications to protein binding, bio-sensing, anti-bacterial and cell cytotoxicity studies.

Biocompatible quantum dots (QDs) have attracted a lot of attention due to their potential biological applications (drug delivery, sensing and diagnosis). Here, we have synthesized 2-4 nm sized biocompatible zinc sulphide (ZnS) QDs using a plant leaf extract as an immobilizing and stabilizing agent via a green route. We have investigated the biological effects of ZnS QDs in a variety of applications, including (1) anti-bacterial activity, (2) cell cytotoxicity, (3) bio-sensing and (4) protein binding. Studies on the anti-bacterial activity of the as-synthesized ZnS QDs against E. coli and E. faecalis inhibited bacterial growth effectively and showed a cytotoxic effect on the HeLa cell line. The biosynthesized ZnS QDs act as a fluorescence probe to detect bilirubin and rifampicin (RFP) with a wide linear range, high sensitivity, good selectivity, and a low limit of detection (LOD), with LOD values of 22.12 ± 0.25 ng mL-1 and 122.37 ± 0.42 ng mL-1, respectively. In a biological matrix, the QDs can form a complex with biomacromolecules; therefore, we studied the interaction between a carrier protein (HSA) and the as-synthesized ZnS QDs. The surface functionalized and nano-sized ZnS-GT QDs were observed to form complexes with the human serum albumin (HSA) protein and quenched the intrinsic fluorescence of HSA through static and dynamic quenching modes. The binding affinity was observed to be of the order of 105 M-1 for the HSA-ZnS-GT QD interactions, which can be considered as a reversible mode of binding. The effect of the ZnS QDs on other ligands and protein interactions was also studied. Enhanced binding affinities for HSA-quercetin ((5.994 ± 0.139) × 105 M-1) and HSA-luteolin ((3.068 ± 0.127) × 105 M-1) interactions were also observed in the presence of ZnS-GT QDs.

Interaction properties of biosynthesized cadmium sulphide quantum dots with human serum albumin: further investigation of antibacterial activities and sensing applications.

The synthesis of small-sized quantum dots (QDs) (1-10 nm) via the green route has garnered great interest regarding their prospective use in many biological applications (diagnosis, drug delivery and in vivo sensing); this is difficult to achieve using chemical synthesis methods, which produce larger size QD particles and also require hazardous reagents. Here, we synthesized biogenic cadmium sulphide (CdS) QDs using green tea extract as the reducing agent to produce particles that were homogeneous and a smaller size of 2-4 nm. We also elucidated the (a) protein binding, (b) antibacterial use and (c) sensing applications of biogenic CdS QDs in this present work. The biosynthesized CdS QDs were found to have extensive antibacterial activity against both Gram-negative Escherichia coli and Gram-positive Enterococcus faecalis bacterial strains. The introduction of QDs in biological medium can lead to the formation of protein-QD complexes; therefore we investigated the binding interaction of CdS QDs with the carrier protein human serum albumin (HSA) in vitro. The synthesized CdS QDs quenched the intrinsic fluorescence of HSA through a static quenching mechanism and the binding constant (Kb ) was in the order of 104 M-1 . It was also observed that the presence of biogenic CdS QDs affected the HSA-ligand interactions in vitro. The synthesized CdS made highly effective sensors for tetracycline, rifampicin, and bilirubin with limit of detection (LOD) values of 99, 141 and 29 ng/ml, respectively.

Molecular recognition of two bioactive coumarin derivatives 7-hydroxycoumarin and 4-methyl-7-hydroxycoumarin by hen egg white lysozyme: Exploring the binding mechanism, thermodynamic parameters and structural changes using multispectroscopic and computational approaches.

Multispectroscopic and computational methods of exploring the interaction between a carrier protein and therapeutic compounds provide a preliminary investigation into establishing the efficacy of such compounds. Here, two coumarin derivatives, 7-hydroxycoumarin (7-HC) and 4-methyl-7-hydroxycoumarin (4-Me-7-HC), were selected to carry out numerous biophysical interaction studies with a model carrier protein, hen egg white lysozyme (HEWL). Fluorescence spectroscopy studies conducted between HEWL and 7-HC/4-Me-7-HC revealed the binding constants (Kb) were in the range of 104 M-1, indicating a moderate nature of binding. The quenching mechanism observed during complexation process was an unusual static quenching due to the effect of temperature on the rate constant. Thermodynamic parameters revealed a positive ΔH and ΔS for HEWL-7-HC/4-Me-7-HC, indicating hydrophobic forces played a dominant role in the interaction process. FRET studies suggested a possible non-radiative energy transfer from the donor (HEWL) to the acceptor (coumarins). Molecular docking studies revealed the interaction of 7-HC/4-Me-7-HC with intrinsic fluorophores, Trp63 and Trp108, Trp108 being an essential residue for binding as proven by molecular dynamic (MD) simulation. MD simulation studies also indicated conformational stability gained by HEWL upon interaction with 7-HC and 4-Me-7-HC. The microenvironment surrounding the Trp residues showed a significant Stoke's shift on carrying out 3-D fluorescence. CD studies revealed a decrease in the alpha helical content of HEWL upon interacting with the ligands. Enzymatic assay conducted for HEWL in the presence of 7-HC/4-Me-7-HC saw an increase in the activity of HEWL, suggesting a change in structural conformation and stability of the protein, altering its activity.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.