Muslim Raza

Size dependent catalytic activities of green synthesized gold nanoparticles and electro-catalytic oxidation of catechol on gold nanoparticles modified electrode

A green and facile method for the synthesis of gold nanoparticles (AuNPs) was developed. Phytochemicals from the aqueous extract of Fagonia indica were used to reduce and stabilize gold precursor (HAuCl4) into gold nanoparticles. Various analytical techniques were used to determine size, morphology, composition, crystallinity, and capping biomolecules of the prepared gold nanoparticles. The appearance of characteristic surface plasmon resonance peak (SPR) at 542–565 nm revealed the synthesis of AuNPs (UV-Vis spectroscopy). XRD and EDX studies confirmed the face centered cubic structure and elemental composition of the green synthesized gold nanoparticles. Average particle sizes of 50, 20, and 70 nm were obtained by using the plant concentrations of 5, 10, and 15 mL respectively, with a fixed amount of HAuCl4 (2 mM). The effect of synthesis variables (amount of plant extract and HAuCl4) on the gold nanoparticles was also studied. Under the optimized conditions (10 mL plant extract + 2 mM HAuCl4 and pH 8) the biogenic gold nanoparticles were well dispersed, small sized (15–20 nm), and mostly hexagonal in shapes. These Fagonia indica mediated Au-nanoparticles were observed to have strong catalytic activity for the photocatalytic reduction of methylene blue and chemical reduction of 4-nitrophenol. 80% of MB could be photodegraded under visible-light irradiation after 80 min, showing the excellent photocatalytic activity of biogenic gold nanoparticles. Moreover, the catalytic activity was found to be size dependent. Cyclic voltammetry (CV) indicated the electrochemical reversible oxidation of catechol at the green synthesized Au-NPs modified glassy carbon electrode. The Au-NPs modified electrode showed excellent catalytic activity with strong stability toward the electrochemical oxidation of catechol.

Suppression of inflammatory response by chrysin, a flavone isolated from Potentilla evestita Th. Wolf. In silico predictive study on its mechanistic effect

Flavonoids are the most abundant natural polyphenols widely distributed in plants. Among them, chrysin has recently attracted the attention for its anti-tumor and anti-oxidant activities and also for its protective effects on allergic inflammation. Therefore, in this study, we set out to investigate and characterize the effects of chrysin in classical models of inflammation reasoning that this would expand our knowledge on the pharmacological properties of this flavone. To this aim we have firstly isolated chrysin from Potentilla evestita Th. Wolf. and successively evaluated its anti-inflammatory and analgesic potential on writhing and formalin test and also on carrageenan-induced paw oedema. Finally, the present study was planned to investigate, by the aim of docking analysis, the molecular interaction of this compound on the binding site of COX-1 and COX-2 enzymes. On writhing test, we observed a significant inhibition of writhings after the administration of chrysin at 5.0 and 10.0 mg/kg i.p. (25.00±9.22% and 55.67±7.62% respectively). On formalin test, the flavone at dose of 10.0 mg/kg i.p. displayed its maximum analgesic and anti-inflammatory effect on both early (35.67±7.88%) and late phase (50.57±5.36%) and similarly displayed at 4h a significant anti-inflammatory effect in carrageenan-induced paw oedema. Moreover, in silico analysis of receptor ligand complex shows that chrysin interacts weakly with COX-1 binding site whereas displayed a remarkable interaction with COX-2. These findings suggest that the flavone chrysin isolated from P. evestita Th. Wolf. possesses in vivo anti-inflammatory and anti-nociceptive potential, which are supported in silico by an interaction with COX-2 binding site.

Isatis tinctoria mediated synthesis of amphotericin B-bound silver nanoparticles with enhanced photoinduced antileishmanial activity: A novel green approach

After malaria, Leishmaniasis is the most prevalent infectious disease in terms of fatality and geographical distribution. The availability of a limited number of antileishmanial agents, emerging resistance to the available drugs, and the high cost of treatment complicate the treatment of leishmaniasis. To overcome these issues, critical research for new therapeutic agents with enhanced antileishmanial potential and low treatment cost is needed. In this contribution, we developed a green protocol to prepare biogenic silver nanoparticles (AgNPs) and amphotericin B-bound biogenic silver nanoparticles (AmB-AgNPs). Phytochemicals from the aqueous extract of Isatis tinctoria were used as reducing and capping agents to prepare silver nanoparticles. Amphotericin B was successfully adsorbed on the surface of biogenic silver nanoparticles. The prepared nanoparticles were characterized by various analytical techniques. UV-Visible spectroscopy was employed to detect the characteristic localized surface plasmon resonance peaks (LSPR) for the prepared nanoparticles. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) studies revealed the formation of spherical silver nanoparticles with an average particle size of 10-20nm. The cubic crystalline structure of the prepared nanoparticles was confirmed by X-ray diffraction (XRD) study. FTIR spectroscopic analysis revealed that plant polyphenolic compounds are mainly involved in metal reduction and capping. Under visible light irradiation, biogenic silver nanoparticles exhibited significant activity against Leishmania tropica with an IC50 value of 4.2μg/mL. The leishmanicidal activity of these nanoparticles was considerably enhanced by conjugation with amphotericin B (IC50=2.43μg/mL). In conclusion, the findings of this study reveal that adsorption of amphotericin B, an antileishmanial drug, to biogenic silver nanoparticles, could be a safe, more effective and economic alternative to the available antileishmanial strategies.

Visible light photo catalytic inactivation of bacteria and photo degradation of methylene blue with Ag/TiO2 nanocomposite prepared by a novel method

Water purification is one of the worldwide problem and most of the conventional methods are associated with a number of drawbacks. Therefore it is the need of the day to develop new methods and materials to overcome the problem of water purification. In this research work we present a simple and green approach to synthesize silver decorated titanium dioxide (Ag/TiO2) nanocomposite with an efficient photo catalytic activities. Phytochemicals of the Cestrum nocturnum leaf extract were used to synthesize silver nanoparticles (AgNPs), Titanium dioxide (TiO2) and Ag/TiO2 nanocomposite. To confirm the formation, crystal structure, particle size and shape of green synthesized nanoparticles and nanocomposite, they were characterized by UV-visible spectroscopy (UV-vis), X-ray diffraction spectroscopy (XRD), high resolution transmission electron microscopy (HRTEM), Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). The AgNPs, TiO2 and Ag/TiO2 were evaluated for photo degradation of methylene blue (MB) and photo inhibition of Bacteria. The bio-synthesized Ag/TiO2 nanocomposite was observed to have strong catalytic activities for photo reduction of MB and photo inactivation of bacteria as compared to bare AgNPs and TiO2. In the presence of Ag/TiO2, 90% of MB was degraded only in 40min of irradiation. Alternatively the bare AgNPs and TiO2 degraded less than 30% and 80% respectively of MB even in more than 100min of irradiation. Similarly the Ag/TiO2 has very strong photo inhibition efficiency towards Escherichia coli and Pseudomonas aeruginosa. The zone of inhibition of irradiated Ag/TiO2 nanocomposites against E. coli and P. aeruginosa was 19mm and 17mm respectively which was two times higher than in dark. These promising photocatalytic activities of nanocomposite may be due to the highly decorated AgNPs over the surface of TiO2.

Biophysical and molecular docking approaches for the investigation of biomolecular interactions between amphotericin B and bovine serum albumin

Exogenous drug as an antidote to treat various infections get absorbed in the blood circulatory system of a human can directly contact with transporter proteins such as serum albumin. Therefore, for rational drug discovery, understanding the biomolecular interaction between drugs and protein is highly important. In this contribution, we describe the possible interactions between an antifungal drug Amphotericin B (AmB) and Bovine Serum Albumin (BSA) using multi-spectroscopic techniques and further confirmed through in-silico approaches. Binding effects of AmB on BSA conformation, surface morphology, topology, and stability were determined by Ultraviolet-visible spectroscopy (UV), Fourier transform infrared spectroscopy (FT-IR), Circular Dichroism (CD), Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Fluorescence Spectroscopy and Molecular dynamic simulations. The Stern-Volmer equation was used to determine the binding site (0.4) and binding constant (8.16×105M-1). The intrinsic intensity of the native BSA was quenched by AmB through static quenching mechanism. The calculated Gibbs free energy value (-8.70kcal/mol) indicated the involvement of hydrogen bonding and hydrophobic contacts in BSA-AmB interaction. The hydrodynamic radii and surface contact area of BSA-AmB molecules are decreasing which can strongly support the stabilizing action of complex particles. Moreover, the finding of this work will provide information for the drug designers to further study the AmB binding mechanism and their pharmacodynamics and pharmacokinetics features in order to achieve better therapeutic efficacy.

Urease inhibitory profile of extracts and chemical constituents of Pistacia atlantica ssp. cabulica Stocks

The current study was designed to evaluate the urease inhibitory profile of extract and fractions of Pistacia atlantica ssp. cabulica Stocks followed by bioactivity-guided isolated compounds. The crude extract was found significantly active with urease inhibitor (95.40% at 0.2 mg/mL) with IC50 values of 32.0 ± 0.28 μg/mL. Upon fractionation, ethyl acetate fraction displayed 100% urease inhibition with IC50 values of 19.9 ± 0.51 μg/mL at 0.2 mg/mL. However, n-hexane and chloroform fractions exhibited insignificant urease inhibition. Similarly, the isolated compound, transilitin (1) and dihydro luteolin (2) demonstrated marked urease attenuation with 95 and 98% respectively, at 0.15 mg/mL. Both the isolated compounds showed marked potency with IC50 values of 8.54 ± 0.54 and 9.58 ± 2.22 μg/mL, respectively. In short, both the extract and fractions and isolated compounds showed marked urease inhibition and thus a useful natural source of urease inhibition. Graphical abstract showing the image Pistacia atlantica, chemical structure of isolated compounds and urease enzyme.

Anti-tumour-promoting and thermal-induced protein denaturation inhibitory activities of β-sitosterol and lupeol isolated from Diospyros lotus L.

In this study, the anti-tumour-promoting and thermal-induced protein denaturation inhibitory activities of β-sitosterol (1) and lupeol (2), isolated from Diospyros lotus L., were explored. Compound 1 showed a marked concentration-dependent inhibition against 12-O-tetradecanoylphorbol-13-acetate (20 ng/32 pmol)-induced Epstein–Barr virus early antigen activation in Raji cells with IC50 of 270 μg/ml, without significant toxicity (70% viability). Compound 2 showed significant anti-tumour-promoting effect with IC50 of 412 μg/ml, without significant toxicity (60% viability). In heat-induced protein denaturation assay, compound 1 exhibited a concentration-dependent attenuation with a maximum effect of 73.5% at 500 μg/ml with EC50 of 117 μg/ml, while compound 2 exhibited a maximum effect of 59.2% at 500 μg/ml with EC50 of 355 μg/ml. Moreover, in silico docking studies against the phosphoinositide 3-kinase enzyme also show the inhibitory potency of these compounds. In short, both the compounds exhibited a marked anti-tumour-promoting and potent inhibitory effect on thermal-induced protein denaturation.

Phosphodiesterase-1 Inhibitory Activity of Two Flavonoids Isolated from Pistacia integerrima J. L. Stewart Galls

Pistacia integerrima is one of twenty species among the genus Pistacia. Long horn-shaped galls that develop on this plant are harvested and used in Ayurveda and Indian traditional medicine to make “karkatshringi”, a herbal medicine used for the treatment of asthma and different disorders of respiratory tract. However, until now, the molecular mechanisms of action of “karkatshringi” and its chemical characterization are partially known. This study deals with the isolation and characterization of the active constituents from the methanolic extract of P. integerrima galls and it was also oriented to evaluate in vitro and in silico their potential enzymatic inhibitory activity against phosphodiesterase-1 (PDE1), a well-known enzyme involved in airway smooth muscle activity and airway inflammation. Our results showed that the methanolic extract of P. integerrima galls and some of its active constituents [naringenin (1) and 3,5,7,4′-tetrahydroxy-flavanone (2)] are able in vitro to inhibit PDE1 activity (59.20 ± 4.95%, 75.90 ± 5.90%, and 65.25 ± 5.25%, resp.) and demonstrate in silico an interesting interaction with this enzymatic site. Taken together, our results add new knowledge of chemical constituents responsible for the biological activity of P. integerrima and contextually legitimate the use of this plant in folk medicine.

Molecular mechanism of tobramycin with human serum albumin for probing binding interactions: multi-spectroscopic and computational approaches

Binding interactions between human serum albumin (HSA) and tobramycin (TOB) under simulated physiological conditions (pH = 7.4) were explored using ultraviolet-visible absorption (UV), Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD), and fluorescence, as well as by computational modeling. Fluorescence quenching of HSA upon TOB addition was found to be a static quenching process, as revealed from the diminishing trend of the Stern–Volmer quenching constant with increasing temperature as well as UV-vis absorption spectral results. Fluorescence quenching value as titration results demonstrated an excellent binding affinity with binding constant Ks (2.06 × 106 M−1) between TOB and HSA. The FTIR and the CD spectra showed secondary and tertiary structural changes in the HSA, whereas three-dimensional fluorescence spectral results disclosed microenvironmental perturbations around aromatic fluorophores upon TOB binding. Competitive site-marker displacement results along with molecular modeling suggested the preferred location of the TOB binding site to be site I, located in subdomain IIA of HSA. The solvent accessible surface area (ASAs) calculations for the native HSA and HSA–TOB displayed a reduction in ASAs, providing strong support for effectiveness of TOB binding to HSA. These findings provide a useful experimental strategy for drug designers to further study the molecular binding mechanisms of TOB to HSA to gain better therapeutic efficacy.

Insights from spectroscopic and in-silico techniques for the exploitation of biomolecular interactions between Human serum albumin and Paromomycin

The study of molecular interactions of drug-protein are extremely important from the biological aspect in all living organisms, and therefore such type of investigation hold a tremendous significance in rational drug design and discovery. In the present study, the molecular interactions between paromomycin (PAR) and human serum albumin (HSA) have been studied by different biophysical techniques and validated by in-silico approaches. The results obtained from Ultraviolet-visible spectroscopy (UV) and Fourier transform infrared spectroscopy (FT-IR) demonstrated a remarkable change upon the complexation of PAR with HSA. Circular Dichroism (CD), Dynamic Light Scattering (DLS) and Resonance Rayleigh scattering (RRS) results revealed a significant secondary structure alteration and reduction of hydrodynamic radii upon the conjugation of PAR with HSA. The fluorescence spectroscopy results also apparently revealed the static quenching mechanism. The number of binding sites, binding constants, and Gibbs free energy values were calculated to illustrate the nature of intermolecular interactions. Similarly, the in-silico docking and molecular dynamics simulation clearly explain the theoretical basis of the binding mechanism of PAR with HSA. The experimental and docking approaches suggested that PAR binds to the hydrophobic cavity site I of HSA. The finding of present investigation will provide binding insight of PAR and associated alterations in the stability and conformation of HSA.