Drug Invention Today最新文献

Eight derivatives of N-(3-chloro-4-fluorophenyl)-2-(5-((3-(4-hydroxy-2, 2-dimethyl l-2,3-dihydrobenzofuran-5-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl) acetamide were synthesized by reacting pyrazole having substitutions at 1 and 3 positions (phenyl and benzofuran) with various substituted N-(3-chloro-4-fluorophenyl)-2-(4-oxo-2-thioxothiazolidin-3-yl)acetamides.The series of reactions are depicted in following scheme. The chemical structures of these compounds were confirmed by means of ¹H NMR, IR and Mass spectra. The compounds were assayed for anti-inflammatory activity.

Among the compounds 10a, 10b and 10d showed significant anti-inflammatory activity, 10c showed moderate anti-inflammatory activity.

Background

In the present study, the lemon pulp and peel along-with their secondary metabolites were studied and compared for its antioxidant activity.

Method

Various in vitro and ex vivo studies were done to estimate the polyphenols and flavonoids present in the lemon pulp and peel. The reducing power, free radical scavenging activity and lipid peroxide inhibition were investigated for the extracts.

Results

The lemon peel was found to have a slightly greater count of polyphenols and flavonoids, showing a difference of 0.2. The peel extracts also showed better reducing power and higher free radical scavenging activity. The peel extracts gave 82.3% of inhibition towards lipid peroxidation, when compared to the pulp extracts which showed an inhibition of 78.2%.

Conclusion

The antioxidant activity was found to be higher in the case of lemon peel when compared to the pulp.

Objective

To investigate the hepatoprotective activity of aqueous and methanol extracts of leaves of Morinda tinctoria Roxb. against paracetamol induced liver damage into rats.

Methods

The hepatoprotective activity aimed for plant extracts was investigated for paracetamol induced hepatotoxicity into rats. Sprague–Dawley rats of either sex were divided into 7 groups of 5 animals each and are given orally the following treatment for 10 days. The normal control was given 1% CMC 1 ml/kg b.w., p.o. Paracetamol at dose of 3 g/kg b.w., p.o. was given as toxic dose for inducing hepatotoxicity. Liv.52 (50 mg/animal, p.o) was given as reference standard. Two different doses of M. tinctoria extracts of both aqueous and methanol (100 mg/kg, p.o, 150 mg/kg, p.o) was tested for hepatoprotective activity. The treatment was given for 10 days and after 48 h of last treatment blood was collected from direct cardiac puncture and analysed for various serum parameter like serum glutamic pyruvic transaminase (SGPT), Serum glutamic oxaloacetic transaminase (SGOT), Total Bilirubin (TB), Direct Bilirubin and Total cholesterol (TC) in different groups.

Results

The phytochemical investigation of the both extracts showed the presence of alkaloids, flavonoids, glycosides, carbohydrates, saponin and tannin and phenols. The paracetamol intoxication lead to histological and biochemical deterioration. The treatment with both aqueous and methanolic leaves extracts of M. tinctoria reduced the level of SGOT, SGPT, TB, DB and TC and also reversed the hepatic damage towards normal which further supports the hepatoprotective activity of leaf extracts of M. tinctoria.

Conclusions

Both aqueous and methanol extracts of leaves of M.tinctoria have significant effect at higher dose of 150mg/kg.b.w.

Background & aim

Pyrimidines represent a broad class of compounds, which have received considerable attention due to their wide range of biological activities such as, anti-inflammatory, COX inhibitor, anticancer, antiallergic and analgesic. On the basis of exhaustive literature review and PASS predictions, it has been found that substituted 1,2,3,4 tetrahydropyrimidine derivatives have good potential to exhibit in vitro anti-inflammatory activity.

Method

The toxicity and pharmacological activities of synthesized compounds were studied with the help of softwares. The non-toxic compounds, which are having Pa (Probable activity), value more than 0.3 & less than 0.5 were synthesized. A novel procedure for synthesis of substituted 1,2,3,4-tetrahydropyrimidine was reported by the reaction of urea (0.01 mmol) and bis(methylthio)methylenemalononitrile (0.01 mmol). Substituted 1, 2, 3, 4-tetrahydropyrimidine possess a replaceable active methylthio group at the 6th position, which was substituted with selected nucleophiles to get final compounds.

Result

All synthesized compounds were characterized by IR, ¹H-NMR, MS and elemental analysis. All compounds were screened for in-vitro anti-inflammatory activity by inhibition of protein denaturation method using diclofenac as a standard drug. The results revealed that almost all the tested compounds showed potent in-vitro anti-inflammatory activity.

Conclusion

The obtained results for anti-inflammatory prove the necessity for further investigation to clarify the features underlying the anti-inflammatory potential of tested compounds. Substituted 1, 2, 3, 4-tetrahydropyrimidine derivatives have potential to design lead for anti-inflammatory activity.

Background

Structure based drug design has revolutionised the way new drug molecules are being looked for. A very important technique in this process is homology modelling of protein structures. Although a number of protocols are proposed by a number of research groups, yet a comparative assessment is desired to identify the relative merits and demerits of these programs. Comparative assessment of various homology modelling tools was evaluated using prediction of structure of B-domain of factor V.

Methods

The methods employed, here, for comparative assessment were ESyPred3D, SWISS MODEL, PHYRE2 and YASARA. The criteria for selection of these tools were their popularity among users and level of automation. All these are completely automated and require only protein sequence or alignments as input. These tools were fast and the results were obtained within few hours.

Results

To evaluate the various models of the protein structures, we carried out exhaustive evaluation through “WHATif” and “QMEAN”. The parameters included the bond angle, bond length, coarse packing quality control, collision symmetry, omega angle, hand check dihedrals etc.

Conclusion

According to our study YASARA emerged as best performer.

Objectives

The aim of the present investigation was to formulate and evaluate Eudragit microspheres for controlled release of glipizide.

Methods

The microspheres were produced by emulsion solvent evaporation method, using the Eudragit RS100, Eudragit RL100 and also by their combination. Further, the prepared microspheres were characterized for the micromeritic properties, drug loading as well as Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy. In vitro release study was performed in phosphate buffer (pH 7.4).

Results and discussion

The microspheres were free flowing in nature. The mean particle size ranged from 112 to 132 μm and the entrapment efficiencies ranged from 43.27 to 61.89%. The entrapment efficiency was found to be dependent on nature of polymer used for formulation. The FTIR confirmed stable character of glipizide in the drug-loaded microspheres. The DSC revealed the uniform dispersion of drug and polymer. Scanning electron microscopy revealed the surface morphology. The mechanism of drug release from the microsphere was found to be non-fickian type.

Conclusion

Eudragit microsphere containing glipizide was prepared successfully by using an emulsion solvent evaporation technique.

Background

Acinetobacter spp. has emerged as a significant hospital pathogen because it is quickly becoming resistant to commonly used routine drugs and is able to survive on various biotic and abiotic surfaces. The main objective of this study is to isolate various clinical strains of Acinetobacter and to analyze its imipenem resistance pattern and biofilm formation.

Materials and methods

Acinetobacter strains were isolated from various clinical isolates. Resistance to imipenem was determined by both disk diffusion and minimum inhibitory concentration (MIC) methods. Biofilm production as a marker of virulence factor was also determined by microtiter plate method.

Results

65 strains of Acinetobacter isolated from various clinical samples. Resistance to imipenem was determined by performing minimum inhibitory concentration (MIC) which showed 46% resistance, compared with disk diffusion i.e. (32.3%). Among 65 strains, 7 were strong biofilm producers, 18 were moderate biofilm producers, 20 were weak biofilm producers and 20 were non biofilm producers. The association of biofilm production and imipenem resistance was found to be statistically significant.

Conclusion

Strains of Acinetobacter showing multi drug resistance and biofilm production remain as a great threat in hospital environment.

Background

Influenza A virus H1N1 causes human influenza (flu) in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. Zanamivir which blocks the function of the viral neuraminidase protein of influenza A virus H1N1, thus preventing the virus from reproducing by budding from the host cell has been reported for having resistance against the virus. The neuraminidase enzyme is a glycoside hydrolase enzyme which is found on the surface. It enables the virus to be released from the host cell and cleave sialic acid groups from glycoproteins and is required for influenza virus replication. The World Health Organization declared the H1N1 influenza pandemic on August 10, 2010.

Methods

The present work focuses on the in silico virtual screening and molecular docking analysis for potential neuraminidase inhibitors using zanamivir like molecules retrieved from the ZINC database. The zanamivir like molecules were further inspected for PASS prediction and ADME-Toxicity analysis using in silico approaches.

Results

Molecular docking results suggest ZINC01696606, ZINC05069324 and ZINC02468939 have better binding affinity than zanamivir and better pharmacological parameters than zanamivir.

Conclusion

Zanamivir like molecules viz. ZINC01696606, ZINC05069324 and ZINC02468939 support experimental testingas zanamivir is reported for having resistance against neuraminidase enzyme and bioavailability problems.

Objective

The aim of present research work was to fabricate and evaluate the Mefenamic acid (MF) loaded Solid lipid nanoparticles (SLNs) using Glyceryl monostearate as lipid and tween 80 as surfactant.

Method

MF loaded SLNs were prepared by Solvent Emulsification diffusion technique. Various batches were prepared by hit and trial method varying drug to lipid ratio and surfactant concentration and evaluated for particle size & distribution, particle morphology, zeta potential, percent drug loading and percent drug entrapment efficiency.

Result

Among various lipids like Glyceryl monostearate, Stearic acid and Palmitic acid, GMS was selected for the fabrication of SLNs it was due to the highest solubility of MF in GMS as compared to other above mentioned lipids. Particle size, polydispersity index (PDI), zeta potential, percent drug loading and percent drug entrapment efficiency were found to be 109.7 nm, 0.34, −20.3 mV, 43.00 and 75.45 respectively. Morphologically the SLNs were found to be spherical with rough surfaces. The optimized formulation exhibited 93.28% cumulative drug release after 24 h, while the release mechanism was found to be Fickian diffusion type.

Conclusion

It is concluded that Solvent Emulsification diffusion technique is suitable for fabrication of MF loaded SLNs. All evaluating parameters of optimized SLNs were found to be in acceptable range.

Objective

The objective of present work is to formulate saquinavir mesylate loaded microparticle by counterion induced aggregation method, employing simultaneous cold temperature and hyperosmotic solution treatment as new and novel technique.

Method

Chitosan was chosen as polycation and smaller molecular electrolytes such as sodium citrate, sodium sulphate and sodium orthophosphate were chosen as polyanions. The resulted aggregated microparticles were subjected to surface morphology, size distribution, in-vitro release and drug excipient interaction study.

Results and discussion

Sodium citrate (SC) and sodium sulphate (SS) were able to form aggregates except sodium orthophosphate (SP), as chitosan forms complexes and depends on pH and pKa of medium. Prepared aggregates were subjected to cold hyperosmotic dextrose solution to provide more mechanical strength. The percentage of entrapped drug was more in SC based microparticle as compared to SS. The SS and SC microparticles had average particle size of 1400 μm and 1200 μm respectively. Also, the SEM study revealed more rough and ridges on surface of SC particle as compared to SS. The higher correlation coefficient (r²) was found with Higuchi's equation for all formulations and formulation SS2 had greater r² value of 0.986 compared to all and obeyed fickian diffusion. There was no such major interaction were found during FTIR and DSC study. In addition, stability study was performed and data showed no significant change in assay value for SS2.

Conclusion

The microparticles prepared by above mentioned method had sufficient mechanical strength and were able to released drug for a period of 30 h. Furthermore in-vivo study and pharmacokinetic study have to carry out.