Modulation of salt stress through application of citrate capped silver nanoparticles and indole acetic acid in maize.

The present study was conducted to determine the effect of indole acetic acid (IAA) and Citrate Capped Silver Nanoparticles (Cit-AgNPs) on various attributes of maize under induced salinity stress. Seeds of the said variety were collected from Cereal Crop Research Institute (CCRI) Pirsabaq, Nowshera, sterilized and sown in earthen pots filled with 2 kg silt and soil (1:2) in triplicates in the green house of the Botany Department, University of Peshawar. Nanoparticles were analyzed by scanning electron microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDX), Thermo-gravimetric analysis (TGA) and Differential thermal analysis (DTA). Results of SEM revealed spherical morphology of Cit-AgNPs while EDX showed various elemental composition. TGA showed dominant weight loss up to 300 °C while the DTA showed major exothermic peaks at 420 °C. High Salinity concentration (80 mM) imposed significant detrimental impacts by reducing the agronomic attributes, photosynthetic pigments, osmolytes and antioxidant enzymes, which was remarkably ameliorated by the foliar application of Cit-AgNPs and IAA. Agronomic attributes including leaf, root and shoot fresh and dry weight was improved by 52-74%, 43-69% and 36-79% in individual as well as combined treatments of IAA and NPs. Photosynthetic pigments were amplified by 35-63%, total osmolytes were augmented by 39-68% and antioxidant enzymes including SOD and POD were boosted by 42-57% and 37-62% respectively, in combined as well as individual application. Conclusively, Cit-AgNPs are considered as salt mitigating entities that enhance the tolerance level of crop plants along with IAA, which may be beneficial for the plants growing in saline stressed environment.

Mannich bases derivatives of 2-Phenyl-5-Benzimidazole sulfonic acid; Synthesis, Characterization, Computational studies and Biological evaluation

Abstract A new series of N-Mannich bases of 2-Phenyl-5-benzimidazole sulfonic acid have been synthesized through amino methylation reaction with secondary amines. The two moieties were held together through a methylene bridge, which comes from formaldehyde (Formalin Solution 37%) used in the reaction. Chemical structures of the newly synthesized compounds have been confirmed using FT-IR, 1HNMR and 13CNMR. Different in vitro assays including Anti-oxidant, Enzyme inhibition, Anti-microbial and Cytotoxicity assay were performed to evaluate the biological potential with reference to the standard drug. Among the synthesized library, compound 3a shows maximum alpha-glucosidase inhibition with an IC50 value of 66.66 µg/ml, compound 3d was found most toxic with LC50 value of 10.17 µg/ml. ADME evaluation studies were performed with the help of Molinspiration online software. Docking calculations were also performed. Given the importance of the nucleus involved, the synthesized compound might find extensive medicinal applications as reported in the literature.

Pharmacological evaluation of the gabapentin salicylaldehyde derivative, gabapentsal, against tonic and phasic pain models, inflammation, and pyrexia.

Gabapentinoids are effective drugs in most animal models of pain and inflammation with variable effects in humans. The current study evaluated the pharmacological activity of gabapentin (GBP) and its salicylaldehyde derivative (gabapentsal; [2-(1-(((2-hydroxybenzylidene) amino) methyl) cyclohexyl) acetic acid]; GPS) in well-established mouse models of nociceptive pain, inflammatory edema, and pyrexia at doses of 25-100 mg/kg. GPS allayed tonic visceral pain as reflected by acetic acid-induced nociception and it also diminished thermally induced nociception as a mimic of phasic thermal pain. Antagonism of GPS-induced antinociceptive activities by naloxone (NLX, 1.0 mg/kg, subcutaneously, s.c), beta-funaltrexamine (ß-FNT, 5.0 mg/kg, s.c), naltrindole (NT, 1.0 mg/kg, s.c), and nor-binaltorphimine (NOR-BNI, 5.0 mg/kg, s.c), and pentylenetetrazole (PTZ-15 mg/kg, intraperitoneally, i.p) implicated an involvement of both opioidergic and GABAergic mechanisms. Tail immersion test was conducted in order to delineate the mechanistic insights of antinociceptive response. Inflammatory edema induced by carrageenan, histamine, or serotonin was also effectively reversed by GPS in a fashion analogous to aspirin (150 mg/kg, i.p), chlorpheniramine (1.0 mg/kg, i.p), and mianserin (1.0 mg/kg, i.p), respectively. Additionally, yeast-induced pyrexia was decreased by GPS in a comparable manner to acetaminophen (50 mg/kg, i.p). These observations suggest that GPS possesses ameliorative properties in tonic, phasic, and tail immersion tests of nociception via opioidergic and GABAergic mechanisms, curbs inflammatory edema, and is antipyretic in nature.

A novel gabapentin analogue assuages neuropathic pain response in chronic sciatic nerve constriction model in rats.

Gabapentin (GBP) is an established drug that has been used in the management of symptoms of neuropathy but it is associated with unwanted side effects such as sedation and motor incoordination. The goal of the study was to find out a drug with greater efficacy and safety for the treatment of neuropathic pain. Our previously synthesized GABA analogue (Gabapentsal, GPS) was tested (25-100 mg/kg, i.p) in chronic constriction injury (CCI) induced nociceptive model of static allodynia, dynamic allodynia, thermal hyperalgesia, mechanical hyperalgesia and cold allodynia in rats (Sprague Dawley). Open field and rotarod tests were performed to assess the impact of GPS on the motor performance of the animals. GBP (100 mg/kg, i.p) was used as a standard for comparison. GPS dose dependently reduced static (P <0.001) and dynamic allodynia (P <0.001), thermal hyperalgesia (P <0.001), mechanical hyperalgesia (P < 0.001) and cold allodynia (P < 0.001). In comparison to GBP, GPS failed to alter any significantly the motor performance of rats in both the open field and rotarod assays. These results suggest that GPS is effective in alleviating nociception in CCI neuropathic pain model but free from the side effect of motor discoordination seen in the treatment with GBP. In conclusion, GPS may prove to be a prospectively more effective and safer option in the management of neuropathic syndromes.

One-Pot Multicomponent Synthesis and Bioevaluation of Tetrahydroquinoline Derivatives as Potential Antioxidants, α-Amylase Enzyme Inhibitors, Anti-Cancerous and Anti-Inflammatory Agents.

Mankind has always suffered from multiple diseases. Therefore, there has been a rigorous need in the field of medicinal chemistry for the design and discovery of new and potent molecular entities. In this work, thirteen tetrahydroquinoline derivatives were synthesized and evaluated biologically for their antioxidant, α-amylase enzyme inhibitory, anti-proliferative and anti-inflammatory activities. SF8 showed the lowest IC50 of 29.19 ± 0.25 µg/mL by scavenging DPPH free radicals. SF5 showed significant antioxidant activity in total antioxidant capacity (TAC) and total reducing power (TRP) assays. SF5 and SF9 showed the maximum inhibition of α-amylase enzyme i.e., 97.47% and 89.93%, respectively, at 200 µg/mL concentration. Five compounds were shortlisted to determine their anti-proliferative potential against Hep-2C cells. The study was conducted for 24, 48 and 72 h. SF8 showed significant results, having an IC50 value of 11.9 ± 1.04 µM at 72 h when compared with standard cisplatin (IC50 value of 14.6 ± 1.01 µM). An in vitro nitric oxide (NO) assay was performed to select compounds for in vivo anti-inflammatory activity evaluation. SF13 scavenged the NO level to a maximum of 85% at 50 µM concentration, followed by SF1 and SF2. Based on the NO scavenging assay results, in vivo anti-inflammatory studies were also performed and the results showed significant activity compared to the standard, acetylsalicylic acid (ASA).

Proniosomes as a Carrier System for Transdermal Delivery of Clozapine.

The current study aimed to formulate the clozapine (CLZ) loaded proniosomal gel (PN) and evaluate it's in vitro release, ex vivo permeation and gel properties. CLZ is a BCS class II drug with low bioavailability of 27% and severe adverse drug reactions (ADRs) due to frequent dosing. Proniosomes offer a versatile pro-vesicular approach with potential in transdermal drug delivery. PN-CLZ gel was prepared by the coacervation phase separation method utilizing span-60, cholesterol and lecithin. Optimization of PN gel was done by hit & trial method and the formulations were characterized for particle size, entrapment efficiency (EE), polydispersity index (PDI) and zeta potential (ZP). The optimized formulation had the highest entrapment efficiency of 90% and the average particle size of approx. 325 nm. PDI reflected homogeneity in the formulation. ZP was -59.76 mV, high enough to indicate a stable formulation. The in vitro release studies manifested a sustained release behavior of clozapine from the proniosomal gel. The ex vivo permeation showed noteworthy permeation of the drug through stratum corneum with a steady state flux of 18.26 ug/cm2/hr. The optimized gel was analyzed for pH, spreadability, bioadhesion and rheology. The results suggested that clozapine could be effectively loaded into proniosomal gel for administration through skin.

Poncirin attenuates CCL4-induced liver injury through inhibition of oxidative stress and inflammatory cytokines in mice.

BACKGROUND: In the present study, the poncirin which is flavonoid-7-o-glycosides (isolated from the Poncirus trifoliata) in nature was evaluated against the Carbon tetra chloride (CCL4)-induced liver injury. The poncirin have been reported for various anti-inflammatory, analgesic activity etc. Based on the previous studies it was anticipated that the poncirin will ameliorate CCL4-induced liver injury. METHODS: The CCL4-induced acute and chronic liver injury model (albino BALB/c mice) was used. Following the induction of the liver injury various parameters such as food and water intake, body weight and weight to dry ratio changes were assessed. Furthermore, various hematological, biochemical parameters and histological studies such as hemotoxylin and eosin (H and E) staining were performed. The poncirin treatment was also evaluated against the pro-inflammatory cytokines such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) using enzyme link immunosorbant assay (ELISA). The Swiss Target prediction software was used to investigate interaction of the poncirin on the various hepatic enzymes. RESULTS: The poncirin treatment markedly improved the behavioral parameters such as food and water intake. The liver weight variation was attenuated and total body was improved markedly. The hematological and biochemical parameters were significantly improved compared to the CCL4 treated groups. The anti-oxidants were induced, while oxidative stress markers were reduced promisingly. The H and E staining showed that poncirin treatment significantly improved the histology of liver compared to the CCL4 treated group. Furthermore, the poncirin treatment also evidently decreased the inflammatory mediators. CONCLUSIONS: The poncirin treatment showed marked improvement in behavioral, biochemical and histological parameters following CCL4-induced liver injury. Additionally, the poncirin treatment also markedly improved the antioxidant enzymes, attenuated the oxidative stress markers and inflammatory cytokines.

Antimicrobial, Cytotoxic, and Antioxidant Potential of a Novel Flavone "6,7,4'-Trimethyl Flavone" Isolated from Wulfenia amherstiana.

Wulfenia amherstiana belongs to the Scrophulariaceae family and various plants of this family are known for their biological activities. The present study was focused on the isolation of bioactive compounds including a novel flavone 6,7,4'-trimethyl flavone (TMF) along with three known flavonoids such as quercetin, rutin, and a steroid ß-sitosterol which were isolated from the ethanolic extract of W. amherstiana (Himalayan Wulfenia) through column chromatography and purified by using HPLC. Their structures were identified and elucidated through electron ionization mass spectroscopy (EIMS), 1DNMR (1H-NMR and 13C-NMR), and 2DNMR (COSY, HMQC, and HMBC) spectroscopy. The antimicrobial activities of this novel compound were evaluated through agar well diffusion method, while antioxidant and cytotoxic activities were assessed through 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging assay and brine shrimp lethality assay, respectively. The NMR data revealed that TMF is a novel compound. TMF showed potential antibacterial and antifungal activities against Staphylococcus aureus (MIC = 128 µg/ml) and Candida albicans (MIC = 128 µg/ml). The cytotoxic potential of TMF was determined from brine shrimp lethality assay with LD50 of 127.01 µg/ml. The free-radical scavenging potential of TMF at various concentrations implicated its strong antioxidant activity in vitro. The results revealed that TMF demonstrated substantial antimicrobial activity against S. aureus and C. albicans, strong antioxidant activity, and moderately cytotoxic activity.

Development and Evaluation of Optimized Thiolated Chitosan Proniosomal Gel Containing Duloxetine for Intranasal Delivery.

Proniosomes offer excellent potential for improved drug delivery, through versatile routes, by overcoming the permeation barriers faced by several drugs. The study was aimed to develop a thiomer gel containing duloxetine proniosomes for the intranasal delivery, improving its bioavailability and brain delivery through olfactory system. Duloxetine-loaded proniosomes were optimized through Design-Expert Software, prepared by coacervation phase separation method and then characterized in vitro for different vesicle features, and permeation enhancement potential using various techniques. The formulation F2, out of all the trials, fulfilled the maximum requisite of highest entrapment efficiency (76.21 ± 1.24%) and minimum vesicle size (223.91 ± 11.07 nm). The F2 was embedded in thiolated chitosan gel rendering it mucoadhesive and further characterized. The in vitro release showed a sustained drug release from the mucoadhesive proniosomal gel with only 54% drug release as compared to that of 71% from proniosome over 8 h, following Higuchi drug release model. Ex vivo permeation studies showed the enhancement ratio for the mucoadhesive proniosomal gel to be 1.86-fold greater than proniosomes, indicating a significant improvement in transmucosal permeation. The results suggest that incorporation of proniosomes into thiolated gel can significantly improve its mucoadhesion and retention time in the nasal cavity for providing a sustained drug release. Thus, gel formulation could be considered as a promising approach for efficient intranasal drug delivery of duloxetine. Graphical Abstract.

Domperidone nanocrystals with boosted oral bioavailability: fabrication, evaluation and molecular insight into the polymer-domperidone nanocrystal interaction.

The aim of this study was to employ experimental and molecular modelling approaches to use molecular level interactions to rationalise the selection of suitable polymers for use in the production of stable domperidone (DOMP) nanocrystals with enhanced bioavailability. A low-energy antisolvent precipitation method was used for the preparation and screening of polymers for stable nanocrystals of DOMP. Ethyl cellulose was found to be very efficient in producing stable DOMP nanocrystals with particle size of 130 ± 3 nm. Moreover, the combination of hydroxypropyl methylcellulose and polyvinyl alcohol was also shown to be better in producing DOMP nanocrystals with smaller particle size (200 ± 3.5 nm). DOMP nanosuspension stored at 2-8 °C and at room temperature (25 °C) exhibited better stability compared to the samples stored at 40 °C. Crystallinity of the unprocessed and processed DOMP was monitored by differential scanning calorimetry and powder X-ray diffraction. DOMP nanocrystals gave enhanced dissolution rate compared to the unprocessed drug substance. DOMP nanocrystals at a dose of 10 mg/kg in rats showed enhanced bioavailability compared to the raw drug substance and marketed formulation. A significant increase in plasma concentration of 2.6 µg/mL with a significant decrease in time (1 h) to reach maximum plasma concentration was observed for DOMP nanocrystals compared to the raw DOMP. Molecular modelling studies provided underpinning knowledge at the molecular level of the DOMP-polymer nanocrystal interactions and substantiated the experimental studies. This included an understanding of the impact of polymers on the size of nanocrystals and their associated stability characteristics.

Biodegradable Ingredient-Based Emulgel Loaded with Ketoprofen Nanoparticles.

Biodegradable materials are extensively employed to design nanocarriers that mimic extracellular environment in arthritis. The aim of this study was to formulate and characterize biocompatible, biodegradable ketoprofen-loaded chitosan-chondroitin sulfate (CHS-CS) nanoparticles with natural ingredients for transdermal applications. Polymers used in the design of nanocarriers are biodegradable and produce synergistic anti-inflammatory effect for the treatment of arthritis. For transdermal application, argan oil-based emulgel is utilized to impart viscosity to the formulation. Furthermore, naturally occurring argan oil synergizes anti-inflammatory effect of formulation and promotes skin penetration. CHS and CS form nanoparticles by polyelectrolyte complex formation or complex coacervation at pH 5.0. These particles were loaded into argan oil-based emulgel. Employing this method, nanoparticles were formulated with particle size in the range of 300-500 nm. These nanocarriers entrapped ketoprofen and showed more than 76% encapsulation efficiency and 77% release of the ketoprofen at pH 7.4 within 72 h. Drug releases from CHS-CS nanoparticles by mechanism of simple diffusion. Nanoparticle-loaded argan oil emulgel significantly enhanced skin penetration of ketoprofen as compared to marketed gel (p < 0.05). Nanocarriers prepared successfully delivered drug through transdermal route using natural ingredients. Graphical abstract ᅟ.

Dexibuprofen nanocrystals with improved therapeutic performance: fabrication, characterization, in silico modeling, and in vivo evaluation.

BACKGROUND: The aim of this study was to prepare and evaluate the impact of polymers on fabricating stable dexibuprofen (Dexi) nanocrystals with enhanced therapeutic potential, using a low energy, anti-solvent precipitation method coupled with molecular modelling approach. METHODS: Dexi nanocrystals were prepared using antisolvent precipitation with syringe pump. Crystallinity of the processed Dexi particles was confirmed using differential scanning calorimetry and powdered X-ray diffraction and transmission electron microscopy. Dissolution of Dexi nanocrystals was compared with raw Dexi and marketed tablets. Molecular modelling study was coupled with experimental studies to rationalise the appropriate polymers for stable Dexi nanocrystals. Antinociceptive study was carried out using balb mice. RESULTS: Combinations of hydroxypropyl methylcellulose (HPMC)-polyvinyl pyrrolidone (PVP) and HPMC-Eudragit (EUD) were shown to be very effective in producing stable Dexi nanocrystals with particle sizes of 85.0±2.5 nm and 90±3.0 nm, and polydispersity of 0.179±0.01, 0.182±0.02, respectively. The stability studies conducted for 90 days demonstrated that nanocrystals stored at 2°C-8°C and 25°C were more stable than those at 40°C. The maximum recovery of Dexi nanocrystals was observed from the formulations using the combination of HPMC-PVP and HPMC-EUD, which equated to 98% and 94% of the nominal active drug content respectively. The saturation solubility of the Dexi nanocrystals was substantially increased to 270.0±3.5 µg/mL compared to the raw Dexi in water (51.0±2.0 µg/mL) and stabilizer solution (92.0±3.0 µg/mL). Enhanced dissolution rate (P<0.05) was observed for the Dexi nanocrystals compared to the unprocessed drug substance and marketed tablets. Dexi nanocrystals produced the analgesic effect at much lower doses (5 mg/kg) than that of control standard, diclofenac sodium (20 mg/kg) and Dexi counterparts (40 mg/kg). CONCLUSION: HPMC-PVP and HPMC-EUD were found the best polymer combination to stabilise Dexi nanocrystals. The Dexi nanocrystals exhibited significant dissolution, solubility and analgesic effect compared to the raw Dexi and the control standard diclofenac sodium.

Report: Palladium glutathione, N-acetylcysteine, D-penicillamine conjugation chemistry.

The metalloelement Palladium has a number of potential Pharmaco-clinical advantages. Palladium compounds have antiviral, antibacterial, neuroprotective and antitumor properties. However studies have also indicated some mild to serious toxic effects of Palladium metalloelements. Biothiols are important antioxidants that provide protection against metals toxicity. The interaction of metalloelements with biothiols can provide valuable information about the level of toxicity of the metalloelements and about the protective role of biothiols thereof. In this piece of work the effect of salt and complexes of Palladium on the status of different thiols (GSH, NAC, and D-Pen) in aqueous medium, were examined, The thiol quantification was carried out using Elman's method through UV-visible spectrophotometry and 1H- NMR. Results of the study performed in aqueous medium showed that level of different thiols depleted after the addition of the inorganic salts and organic complexes of Palladium. The mechanism of interaction of Palladium with thiols was examined using H-NMR. The results indicate that the depletion in the level of thiols may be due to 1:1 or 1:2 conjugation of Palladium with thiols. These conjugation reactions further suggest that the Palladium have xenobiotic nature causing oxidative stress and thiols play their role in detoxification and biotransformation of these metalloelements.

Formulation, Evaluation and release rate characteristics of medicated jelly of vitamin C.

Medicated jelly formulations are patient friendly dosage form for pediatric, geriatric and dysphagic patients. These formulations offer rapid dissolution and absorption of drugs through oral mucosa therefore show the early onset of action. The objective of the study was to develop and evaluate oral jelly formulations of vitamin C. Slurry method was adopted using glucose 103gm, sugar 67gm, gelatin 10gm and sorbitol 6.56gm. Preformulation studies were performed including the organoleptic profile, pH, and solubility of both drugs. The medicated jelly of Vitamin C was prepared and evaluated for physical characteristics, weight variation, syneresis, pH, taste and palatability, drug content, release rate characteristics and stability studies. All the jellies were found to have patient welcoming taste and were palatable. All formulations showed more than 50% drug release within 15 minutes, while 93% drug was released in 30 minutes. The results of release kinetics showed that the formulation followed the zero order release kinetics. Thus the drug was released at constant rate independent of the drug concentration involved in the process. All the medicated jellies were found to remain stable stored for 60 days at different temperatures. The present study revealed that medicated jellies of vitamin C could be employed orally in an effective form as an alternative solid oral dosage form for special population such as pediatrics, geriatrics and patients with dysphagia.

Effects of Luteolin and Quercetin in Combination with Some Conventional Antibiotics against Methicillin-Resistant Staphylococcus aureus.

The present study was designed to evaluate the effects of flavonoids luteolin (L) and quercetin + luteolin (Q + L) in combination with commonly used antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates and S. aureus (ATCC 43300). Minimum inhibitory concentrations (MICs) of L and Q + L, as well as the MICs of flavonoids in combination with antibiotics were determined and results showed an increased activity of flavonoids with antibiotics. The synergistic, additive, or antagonistic relationships between flavonoids (L and Q + L) and antibiotics were also evaluated, and additive and synergistic effects were observed for some antibiotic + flavonoid combinations. In addition, some combinations were also found to damage the bacterial cytoplasmic membrane, as assessed through potassium leakage assay. The effects of flavonoids and flavonoids + antibiotics on mecA gene mutations were also tested, and no functional variation was detected in the coding region.

Study of the effect of inorganic and organic complexes of arsenic metal on the status of GSH in T. cells and B. cells of blood.

Arsenic is a major threat to large part of the population due to its carcinogenic nature. The toxicity of Arsenic varies with its chemical form and oxidation states. Glutathione (GSH), a major intra-cellular tripeptide plays a major role in arsenic detoxification. The present study was designed to provide insight into the extent of changes in GSH level by inorganic arsenic in the form of Arsenic trioxide (ATO) and organic arsenic in the form of nitro benzene arsenic acid (NBA). Lymphocytes (T.cells and B.cells) were investigated for determination of change in GSH metabolic status caused by arsenic. The depletion of GSH level positively correlated with increasing arsenic concentration and time of incubation. The decline in GSH level was consistent with increasing pH and physiological temperature. Our findings show that changes in GSH status produced by Arsenic could be due to adduct (As-(SG)3) formation. This change in GSH metabolic status provides information regarding mechanism of toxicity of inorganic and organic arsenicals. These findings are important for the rational design of antidote for the prevention of arsenic induced toxicity.

Molecular interactions of 4-acetoxy-plakinamine B with peripheral anionic and other catalytic subsites of the aromatic gorge of acetylcholinesterase: computational and structural insights.

CONTEXT: A steroidal alkaloid, 4-acetoxy-plakinamine B (4APB), is a recently discovered marine natural product with inhibitory effect against acetylcholinesterase (AChE), but its mechanism of interaction with the enzyme remains to be elucidated. OBJECTIVE: The main objective was to study molecular binding mode of the compound, its interactions with catalytic subsites and molecular mechanism behind its significant inhibitory effect. MATERIALS AND METHODS: All possible interactions of ligands in the binding sites were analyzed using FRED 2.1 and the OMEGA pre-generated multi-conformer library. RESULTS: Dipole-dipole interactions were observed between the secondary amino group of 4APB and Ser200 at a distance of 3.91 Å and also with Gly117 and Gly118. A further dipole-dipole interaction was between Arg289 and the heterocyclic nitrogen. Hydrogen bonding interactions were observed between Tyr130 and secondary amino and C-4 acetyl groups as well as between heterocyclic nitrogen and Phe288 at a distance of 3.04 Å. Hydrophobic interactions were evident between rings C/D of 4APB and with Phe288, Phe330 and Phe331. The computational studies revealed 4APB's critical molecular interaction with amino acids of peripheral active (PAS) and anionic (AS) subsites. DISCUSSION: Our data provided molecular evidence for the mixed competitive inhibitory effect of 4APB. For lead optimization, structural insights revealed the N-methyl group of 4APB could be replaced by NH2 moiety to generate a more favorable hydrogen bonding with Glu199. A polar group insertion such as NH2 or OH at certain sites of the 4APB skeleton is also recommended. CONCLUSION: These computational insights explained the mixed-competitive enzyme kinetic behavior of 4APB. This study outlines a strategy for designing novel derivatives of 4APB with potentially better AChE inhibitory activities through interaction at the PAS and AS sites.

Change in metabolic status of glutathione by palladium nitrate in blood components.

This piece of research work present the toxicological impact of varied concentrations of palladium nitrate [Pd (NO3)2] by changing the chemical status of glutathione and the way how glutathione plays its role in detoxification and conjugation processes of [Pd (NO(3))(2))] in whole blood components (plasma and cytosolic fraction). The impact of different concentration of [Pd (NO3)2] on reduced glutathione level in whole blood component (plasma and cytosolic fraction) were measured spectrophotometrically following Standard Ellman's method. Compared with control sample, significant decrease in the GSH content in whole blood components (plasma and cytosolic fraction) was obtained with various concentrations (100µM-1000µM) of palladium nitrate. Depleted GSH level was more pronounced with time incubation period (0-90) minutes. These finding shows that changes in the GSH status produced by palladium nitrate could either be due to palladium nitrate and glutathione( Pd-SG) complex formation or by conversion of reduce glutathione (2GSH + Pd(+2) - GSSG). This change in the GSH metabolic status provides information regarding the mechanism of palladium, in blood components.