Green synthesized silver nanoparticles of Terminalia bellirica leaves extract: synthesis, characterization, in-silico studies, and antimalarial activity.

Malaria is a mosquito-borne infectious disease that is caused by the Plasmodium parasite. Most of the available medication are losing their efficacy. Therefore, it is crucial to create fresh leads to combat malaria. Green silver nanoparticles (AgNPs) have recently attracted a lot of attention in biomedical research. As a result, green mediated AgNPs from leaves of Terminalia bellirica, a medicinal plant with purported antimalarial effects, were used in this investigation. Initially, cysteine-rich proteins from Plasmodium species were studied in silico as potential therapeutic targets. With docking scores between -9.93 and -11.25 kcal/mol, four leaf constituents of Terminalia bellirica were identified. The green mediated silver nanoparticles were afterward produced using leaf extract and were further examined using UV-vis spectrophotometer, DLS, Zeta potential, FTIR, XRD, and FESEM. The size of synthesized TBL-AgNPs was validated by the FESEM results; the average size of TBL-AgNPs was around 44.05 nm. The zeta potential study also supported green mediated AgNPs stability. Additionally, Plasmodium falciparum (3D7) cultures were used to assess the antimalarial efficacy, and green mediated AgNPs could effectively inhibit the parasitized red blood cells (pRBCs). In conclusion, this novel class of AgNPs may be used as a potential therapeutic replacement for the treatment of malaria.

Synthesis of Indole-Linked Thiadiazoles and their Anticancer Action against Triple-Negative Breast Cancer.

With a lack of targeted therapy and significantly high metastasis, heterogeneity, and relapse rates, Triple-Negative Breast Cancer (TNBC) offers substantial treatment challenges and demands more chemotherapeutic interventions. In the present study, indole-endowed thiadiazole derivatives have been synthesized and screened for antiproliferative potency against the triple-negative breast cancer MDA-MB-231 cell line. Compound 4 h, possessing chlorophenyl moiety, displays the best anticancer potency (IC50: 0.43 µM) in the cell viability assay. The title compounds demonstrate substantial docking competency against the EGFR receptor (PDB ID: 3POZ), validating their in-vitro ant proliferative action. With a high docking score (-9.9 to -8.7 kcal/mol), the indole hybrids display significant binding propensity comparable to the co-crystallized ligand TAK-285 and occupy a similar strategic position in the active domain of the designated receptor. The quantum and electronic properties of the integrated templates are evaluated through DFT, and optimal values of the deduced global reactivity indices, such as energy gap, electronegativity, ionization potential, chemical potential, electrophilicity, etc., suggest their apt biochemical reactivity. The indole hybrids show near-appropriate pharmacokinetic efficacy and bioavailability in the in-silico studies, indicating their candidacy for potential drug usage. Promising in-vitro anticancer action and binding interfaces project indole conjugates as potential leads in addressing the TNBC dilemma.

Imidazo[2,1-b]thiazole based indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor: Structure based design, synthesis, bio-evaluation and docking studies.

Indoleamine-2,3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme known to catalyse the initial and rate limiting step of kynurenine pathway of l-tryptophan metabolism. IDO1 enzyme over expression plays a crucial role in progression of cancer, malaria, multiple sclerosis and other life-threatening diseases. Several efforts over the last two decades have been invested by the researchers for the discovery of different IDO1 inhibitors and the plasticity of the IDO1 enzyme ligand binding pocket provide ample opportunities to develop new heterocyclic scaffolds targeting this enzyme. In the present work, based on the X-ray crystal structure of human IDO1 coordinated with few ligands, we designed and synthesized new fused heterocyclic compounds and evaluated their potential human IDO1 inhibitory activity (compound 30 and 41 showed IC50 values of 23 and 13 µM, respectively). The identified HITs were observed to be non-toxic to HEK293 cells at 100 µM concentration. The observed activity of the synthesized compounds was correlated with the specific interactions of their structures at the enzyme pocket using docking studies. A detailed analysis of docking results of the synthesized analogues as well as selected known IDO1 inhibitors revealed that most of the inhibitors have some reasonable docking scores in at least two crystal structures and have similar orientation as that of co-crystal ligands.

Antibacterial, antioxidant, and haemolytic potential of silver nanoparticles biosynthesized using roots extract of Cannabis sativa plant.

In this study, Cannabis sativa roots extract has been employed for the biosynthesis of silver nanoparticles (AgNPs). The appearance of reddish-brown colour followed by absorption peak of AgNPs at 408 nm through UV-vis spectrophotometry suggested biosynthesis of AgNPs. The size of the particles ranged from 90-113 nm, confirmed using DLS and TEM along with zeta potential of -25.3 mV. The FTIR provided information regarding the phytochemical capping. The study was further elaborated for determining AgNPs antibacterial, antioxidant, and cellular toxicity using MIC, DPPH, MTT, and haemolytic assays, respectively. The AgNPs were significantly effective against Staphylococcus aureus (Gram-positive), as compared to that of Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli (Gram-negative). AgNPs also exhibited remarkable antioxidant potential wherein 58.01 ± 0.09% free radical scavenging was observed at a concentration of 100 µg/ml. AgNPs revealed lower cytotoxicity where cell viability was observed to be 52.38 ± 0.6% at a very high concentration of 500 µg/ml in HEK 293 cells. Further, very low toxicity was seen in RBCs i.e. 6.47 ± 0.04% at a high concentration of 200 µg/ml. Thus, the current study beholds anticipation that Cannabis sativa ethanolic root extract-mediated AgNPs may play a vital role in therapeutic.

Synthesis and inhibition studies towards the discovery of benzodiazepines as potential antimalarial compounds.

The target-based discovery of therapeutics against apicoplast, an all-important organelle is an overriding perspective. MEP pathway, an accredited drug target provides an insight into the importance of apicoplast in the survival of the parasite. In this study, we present the rational design strategy employing sustainable catalysis for the synthesis of benzodiazepine (BDZ) conformers followed by their biological evaluation as prospective inhibitors against the potential target of the IPP pathway, 1-deoxy-D-xylulose-5-phosphatereductoisomerase (DXR). The study reported the inhibitory profile of 8c and 6d against the quintessential step of the only drug target in the erythrocytic stages of parasite development. The potential compounds were identified to represent a novel class of inhibitors that serve as the lead molecules to impede the pathway and further affect the survival of the parasite.

Exploring the Antibacterial and Antibiofilm Efficacy of Silver Nanoparticles Biosynthesized Using Punica granatum Leaves.

The current research work illustrates an economical and rapid approach towards the biogenic synthesis of silver nanoparticles using aqueous Punica granatum leaves extract (PGL-AgNPs). The optimization of major parameters involved in the biosynthesis process was done using Box-Behnken Design (BBD). The effects of different independent variables (parameters), namely concentration of AgNO3, temperature and ratio of extract to AgNO3, on response viz. particle size and polydispersity index were analyzed. As a result of experiment designing, 17 reactions were generated, which were further validated experimentally. The statistical and mathematical approaches were employed on these reactions in order to interpret the relationship between the factors and responses. The biosynthesized nanoparticles were initially characterized by UV-vis spectrophotometry followed by physicochemical analysis for determination of particle size, polydispersity index and zeta potential via dynamic light scattering (DLS), SEM and EDX studies. Moreover, the determination of the functional group present in the leaves extract and PGL-AgNPs was done by FTIR. Antibacterial and antibiofilm efficacies of PGL-AgNPs against Gram-positive and Gram-negative bacteria were further determined. The physicochemical studies suggested that PGL-AgNPs were round in shape and of ~37.5 nm in size with uniform distribution. Our studies suggested that PGL-AgNPs exhibit potent antibacterial and antibiofilm properties.

PGMD/curcumin nanoparticles for the treatment of breast cancer.

The present study aims at developing PGMD (poly-glycerol-malic acid-dodecanedioic acid)/curcumin nanoparticles based formulation for anticancer activity against breast cancer cells. The nanoparticles were prepared using both the variants of PGMD polymer (PGMD 7:3 and PGMD 6:4) with curcumin (i.e. CUR NP 7:3 and CUR NP 6:4). The size of CUR NP 7:3 and CUR NP 6:4 were found to be ~ 110 and 218 nm with a polydispersity index of 0.174 and 0.36, respectively. Further, the zeta potential of the particles was - 18.9 and - 17.5 mV for CUR NP 7:3 and CUR NP 6:4, respectively. The entrapment efficiency of both the nanoparticles was in the range of 75-81%. In vitro anticancer activity and the scratch assay were conducted on breast cancer cell lines, MCF-7 and MDA-MB-231. The IC50 of the nanoformulations was observed to be 40.2 and 33.6 µM at 48 h for CUR NP 7:3 and CUR NP 6:4, respectively, in MCF-7 cell line; for MDA-MB-231 it was 43.4 and 30.5 µM. Acridine orange/EtBr and DAPI staining assays showed apoptotic features and nuclear anomalies in the treated cells. This was further confirmed by western blot analysis that showed overexpression of caspase 9 indicating curcumin role in apoptosis.

Diosgenin Loaded Polymeric Nanoparticles with Potential Anticancer Efficacy.

This study aims to determine the anticancer efficacy of diosgenin encapsulated poly-glycerol malate co-dodecanedioate (PGMD) nanoparticles. Diosgenin loaded PGMD nanoparticles (variants 7:3 and 6:4) were synthesized by the nanoprecipitation method. The synthesis of PGMD nanoparticles was systematically optimized employing the Box-Behnken design and taking into account the influence of various independent variables such as concentrations of each PGMD, diosgenin and PF-68 on the responses such as size and PDI of the particles. Mathematical modeling was done using the Quadratic second order modeling method and response surface analysis was undertaken to elucidate the factor-response relationship. The obtained size of PGMD 7:3 and PGMD 6:4 nanoparticles were 133.6 nm and 121.4 nm, respectively, as measured through dynamic light scattering (DLS). The entrapment efficiency was in the range of 77-83%. The in vitro drug release studies showed diffusion and dissolution controlled drug release pattern following Korsmeyer-Peppas kinetic model. Furthermore, in vitro morphological and cytotoxic studies were performed to evaluate the toxicity of synthesized drug loaded nanoparticles in model cell lines. The IC50 after 48 h was observed to be 27.14 µM, 15.15 µM and 13.91 µM for free diosgenin, PGMD 7:3 and PGMD 6:4 nanoparticles, respectively, when administered in A549 lung carcinoma cell lines.

A Study on Impact of BPA in the Adipose Tissue Dysfunction (Adiposopathy) in Asian Indian Type 2 Diabetes Mellitus Subjects.

A surge to increase the production via usage of chemicals at both industrial and agricultural arena has forced humans to be routinely and imprudently exposed to a wide variety of endocrine disrupting chemicals. The overall aim of the study was to evaluate possible relation that might exist between bisphenol-A (BPA) and the adipose tissue hormones, and further impact on adiposopathy. In the present study, the role of BPA, an "endocrine disruptor" with respect to adiposopathy was evaluated in type 2 diabetes mellitus patients. For the study, 150 healthy control subjects and 150 newly diagnosed diabetes patients were recruited. Fasting venous blood samples was analyzed for several biochemical parameters such as serum glucose, lipid profile, insulin, adiponectin, leptin, TNF-α, IL-6, IL-1, free fatty acid. Concentrations of BPA were also measured both in control and diabetic subjects. Serum BPA concentration was found to be significantly higher in diabetic subjects in comparison to the control subjects. Levels of BPA were found to be positively correlated with BMI and WC in diabetic subjects. Also, it was found to be positively correlated with leptin and negatively correlated with adiponectin in diabetic subjects. Therefore, the current study suggested more deleterious effect of BPA on diabetes and its pathophysiology.

Poly-(Lactic-co-Glycolic) Acid Nanoparticles for Synergistic Delivery of Epirubicin and Paclitaxel to Human Lung Cancer Cells.

Combination therapy using chemically distinct drugs has appeared as one of the promising strategies to improve anticancer treatment efficiency. In the present investigation, poly-(lactic-co-glycolic) acid (PLGA) nanoparticles electrostatically conjugated with polyethylenimine (PEI)-based co-delivery system for epirubicin and paclitaxel (PLGA-PEI-EPI-PTX NPs) has been developed. The PLGA-PEI-EPI-PTX NPs exhibited a monodispersed size distribution with an average size of 240.93 ± 12.70 nm as measured through DLS and 70.8-145 nm using AFM. The zeta potential of 41.95 ± 0.65 mV from -17.45 ± 2.15 mV further confirmed the colloidal stability and PEI modification on PLGA nanoparticles. Encapsulation and loading efficiency along with in vitro release of drug for nanoparticles were done spectrophotometrically. The FTIR analysis of PLGA-PEI-EPI-PTX NPs revealed the involvement of amide moiety between polymer PLGA and PEI. The effect of nanoparticles on the cell migration was also corroborated through wound healing assay. The MTT assay demonstrated that PLGA-PEI-EPI-PTX NPs exhibited considerable anticancer potential as compared to the naïve drugs. Further, p53 protein expression analysed through western blot showed enhanced expression. This study suggests that combination therapy using PLGA-PEI-EPI-PTX NPs represent a potential approach and could offer clinical benefits in the future for lung cancer patients.

Aryldiazoquinoline based multifunctional small molecules for modulating Aß42 aggregation and cholinesterase activity related to Alzheimer's disease.

Research continues to find a breakthrough for the treatment of Alzheimer's Disease (AD) due to its complicated pathology. Presented herein is a novel series of arydiazoquinoline molecules investigated for their multifunctional properties against the factors contributing to Alzheimer's disease (AD). The inhibitory properties of fourteen closely related aryldiazoquinoline derivatives have been evaluated for their inhibitory effect on Aß42 peptide aggregation. Most of these molecules inhibited Aß42 fibrillation by 50-80%. Selected molecules were also investigated for their binding behaviour to preformed Aß40 aggregates indicating a nanomolar affinity. In addition, these compounds were further investigated as cholinesterase inhibitors. Interestingly, some of the compounds turned out to be moderate in vitro inhibitors for AChE activity with IC50 values in low micro molar range. The highest anti-AChE activity was shown by compound labelled as 2a with an IC50 value of 6.2 µM followed by 2b with IC50 value of 7.0 µM. In order to understand the inhibitory effect, binding of selected molecules to AChE enzyme was studied using molecular docking. In addition, cell toxicity studies using Neuro2a cells were performed to assess their effect on neuronal cell viability which suggests that these molecules possess a non-toxic molecular framework. Overall, the study identifies a family of molecules that show good in vitro anti-Aß-aggregation properties and moderately inhibit cholinesterase activity.

Enhancement effects of process optimization technique while elucidating the degradation pathways of drugs present in pharmaceutical industry wastewater using Micrococcus yunnanensis.

Pharmaceutical effluents released from industries are accountable to deteriorate the aquatic and soil environment through indirect toxic effects. Microbes are adequately been used to biodegrade pharmaceutical industry wastewater and present study was envisaged to determine biodegradation of pharmaceutical effluent by Micrococcus yunnanensis. The strain showed 42.82% COD (Chemical oxygen demand) reduction before optimization. After applying Taguchi's L8 array as an optimization technique, the biodegradation rate was enhanced by 82.95% at optimum conditions (dextrose- 0.15%, peptone 0.1%, inoculum size 4% (wv-1), rpm 200, pH 8 at 25 °C) within 6 h. The confirmation of pharmaceuticals degradation was done by 1H NMR (Nuclear magnetic resonance) studies followed by elucidation of transformation pathways of probable drugs in the effluent through Q-Tof-MS (Quadrupole Time of Flight- Mass Spectrometry). The cytotoxicity evaluation of treated and untreated wastewater was analyzed on Human Embryonic Kidney (HEK 293) cells using Alamar Blue assay, which showed significant variance.

Polyphosphate recovery by a native Bacillus cereus strain as a direct effect of glyphosate uptake.

Seven bacterial strains isolated from a glyphosate-exposed orange plantation site were exposed to 1 mM N-(phosphonomethyl)glycine supplied as a phosphorus source. While some exhibited good biodegradation profiles, the strain 6 P, identified as Bacillus cereus, was the only strain capable of releasing inorganic phosphate to the culture supernatant, while accumulating polyphosphate intracellularly along the experimentation time. The composition and purity of the intracellular polyphosphate accumulated by the strain 6 P were confirmed by FTIR analysis. To date, the biological conversion of glyphosate into polyphosphate has not been reported. However, given the importance of this biopolymer in the survival of microorganisms, it can be expected that this process could represent an important ecological advantage for the adaptation of this strain to an ecological niche exposed to this herbicide. The polyphosphate production yield was calculated as 4 mg l-1, while the glyphosate biodegradation kinetic constant was calculated on 0.003 h-1 using the modified Hockey-Stick first-order kinetic model, with a half-life of 279 h. Our results suggest that B. cereus 6 P is a potential candidate for the generation of an innovative biotechnological process to produce polyphosphate through the biodegradation of the herbicide glyphosate.

Versatile biomedical potential of biosynthesized silver nanoparticles from Acacia nilotica bark.

The present study reports the development of potent silver nanoparticles (AgNPs) using bark extract of Acacia nilotica and evaluation of its wound healing, anti-biofilm, anti-cancer and anti-microbial activity. Stable, small sized nanoparticles with spherical morphology were obtained after significant optimization studies that was evaluated through UV-visible spectroscopy. Thereafter, physicochemical characterization of biosynthesized AgNPs was carried out through DLS and FESEM for evaluation of size. EDAX and FTIR were carried out for the evaluation of composition and possible functional groups involved in the reduction and capping of AgNPs. The antibacterial potential was investigated through disc diffusion assay against Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa). Further, the Congo Red Assay (CRA) successfully revealed the anti-biofilm activity against Bacillus subtilis (B. subtilis), Staphylococcus aureus (S. aureus), Proteus vulgaris (P. vulgaris), Pseudomonas aeruginosa (P. aeruginosa). Alamar blue assay was conducted in A549 cells to reveal the remarkable anticancer activity of biosynthesized AgNPs that resulted in a very appreciable manner. Further, the wound healing activity of AgNPs can heal the excised wound of mice up-to 100% within 15 days. All these studies suggested that our biosynthesized AgNPs possess versatile biomedical application.

Catalytic, antibacterial and antibiofilm efficacy of biosynthesised silver nanoparticles using Prosopis juliflora leaf extract along with their wound healing potential.

The present study focuses on the catalytic, antibacterial and antibiofilm efficacy of silver nanoparticles (AgNPs) in an easy, rapid and eco-friendly pathway. Herein, we have synthesised AgNPs using an aqueous extract of P. juliflora leaf. The bioactive compounds present in the extract are responsible for the reduction of Ag+ to Ag0. The particle synthesis was first observed by visual color change and then characterized using UV-visible spectroscopy to confirm the formation of AgNPs. The synthesis conditions were then optimised using critical parameters such as reaction time, AgNO3 concentration, extract to AgNO3 ratio and temperature of the reaction. The hydrodynamic size of the AgNPs with Dynamic light scattering (DLS) was 55.24 nm, while, was in the range of 10-20 nm as determined through Transmission Electron Microscopy (TEM). Further, Fourier transform infrared spectroscopy (FTIR) studies were conducted to discern the functional groups or compounds responsible for the reduction of silver nitrate as well as the capping of silver nanoparticles. Later, X-ray diffraction (XRD) results showed crystalline nature of the biosynthesized AgNPs. To evaluate their antibacterial potential, AgNPs were assessed through disc-diffusion assay, which resulted in an appreciable dose-dependent activity. The antibacterial potential was investigated through disc-diffusion assay against E. coli and P. aeruginosa. The Congo red agar (CRA) plate assay successfully revealed the anti-biofilm activity against B. subtilis and P. aeruginosa. Further, the catalytic activity of synthesised AgNPs was assessed against azo dyes such a Methylene Blue (MB) and Congo Red (CR) that resulted in its effective degradation of toxic compounds in a short span of time. Further, AgNPs were assessed for their wound healing potential.

Evaluation of Anticancer activity of Silver Nanoparticles on the A549 Human lung carcinoma cell lines through Alamar Blue Assay.

Silver nanoparticles have been widely studied to possess antimicrobial as well as anticancer activity, and have found its applications in various fields including pharmaceutical industry, diagnostics, drug delivery, food industry, and others. For this purpose, several cell proliferation assays are widely used for the evaluation of anticancer activity of synthetic compounds as well as natural plant extracts. In general, a compound is said to possess an anticancer activity if it prevents the cancer cells to grow and divide actively, and indirectly activates the generic program of cell death. In this protocol, Alamar blue and MTT assay are described for the analysis of metabolic function and health of the cell. These procedures are generally used for the endpoint analysis. A549 cells are seeded in a 96-well plate, and after the adherence of the cells, they are treated with different concentrations of silver nanoparticles. Followed by 24 h of incubation, colorimetric dyes are added to the wells, and the absorbance is recorded to quantify the percentage cytotoxicity in the sample wells.

Bile Acid Oligomers and Their Combination with Antibiotics To Combat Bacterial Infections.

The ever-growing risk of bacterial resistance is a critical concern. Among the various antimicrobial resistant bacterial strains, methicillin and vancomycin resistant Staphylococcus aureus are among the most dreadful, causing serious complications. On the basis of the hypothesis that microbes have reduced ability to develop resistance against membrane targeting antibiotics, bile acid oligomers having unique facially amphiphilic topologies were designed and synthesized. The oligomers with specific linkers exhibited potent and selective antibacterial activity against Gram-positive bacteria. The lead compounds also improved the efficacy of a range of known antibiotics belonging to different classes when tested in combination. The active dimers were found to be effective against antibiotic-resistant clinical isolates of S. aureus, including multidrug resistant isolates. A significant inhibitory activity against S. aureus biofilm, a highly drug-resistant bacterial phenotype often unresponsive to antibiotic therapy, was also noticed. No adverse effects were observed by these dimers in a cell viability assay against HEK293 cells.