Posted by admin on Sep 30, 2017 in |
Rheumatoid arthritis is a chronic autoimmune disease affecting 1% of the world wide population. Recent researches suggested that the need for discovery of new therapeutic disease modifying anti-rheumatoid arthritis drugs (DMARD’s). BTK (Bruton’s tyrosine kinase) is cytoplasmic, non receptor tyrosine kinase and it is efficient target for the treatment of rheumatoid arthritis. This encouraged us to design a novel series of potent BTK inhibitor. The BTK inhibitor containing five features of Pharma-cophore, One Hydrogen bond donor (HBD), one hydrogen bond acceptor lipid (HBAL) and three hydrophobic features (HYP). Five different ligands containing 4, 5-di-substituted imidazole as heterocyclic nucleus have been designed and optimized by using Molecular docking, Lipinski rule of five and toxicity prediction (ADMET). The optimized ligands were synthesized based on the synthetic feasibility and characterized by using different spectral studies such as IR, 1H NMR, 13C NMR and GC-MS. The synthesized compounds were evaluated for their in vitro Anti-arthritic activity using protein denaturation method and all were found to exhibit an effective inhibition against the protein. Out...
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Posted by admin on Sep 30, 2017 in |
Acquired immune deficiency syndrome (AIDS), one of the most challenging diseases world-wide is caused by human immunodeficiency virus (HIV), member of human retrovirus family. Various therapies and treatments of HIV are provided, but these are rapidly drug resistance in recent decades. After the explosion of HIV integrase (enzyme essential for the replication of DNA virus in the host genome), pharmacoinformatic approaches have become necessary to find target proteins and potential lead compounds. In the current study, identification of novel lead compounds for the HIV-1 integrase enzyme is done using different chemometric techniques. A set of 26 compounds obtained from literature are used for the ADMET prediction using DruLiTo software. The FlexX score of the compo-unds C2 and C10, fitting all the ADMET properties, with the target protein is found to be – 8.0 and – 18.4 respectively. These ligands are further analysed for the core replacement studies using ReCore module of LeadIt software which gave two novel compounds from Zinc database qualifying the ADMET properties with FlexX score of...
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Posted by admin on Sep 30, 2017 in |
Stress plays a major role in various pathophysiological processes related with neurodegenerative diseases and mental disorders. Zebrafish has emerged as a promising model organism in inducing Chronic Unpredictable Stress (CUS). In the present study, we have attempted to understand the molecular basis of neuronal changes underlying CUS in zebrafish model. An evidence for a connection between CUS and apoptosis in the brain of zebrafish was analyzed. For this purpose, zebrafish were subjected to CUS protocol twice a day for a period of 15 days. The impact of CUS on the brain was evaluated in relation to the expression of the stress marker genes: corticotropin releasing factor (crf) and glucocorticoid receptor (gr). The effects of CUS were also estimated from the expression of p53 mediated apoptotic genes: p53, noxa, bcl2 and casp3. CUS protocol increased the gene expression of crf (p<0.05) and decreased the expression of gr (p<0.05). The impact of CUS on the apoptotic pathway showed increased expression of p53 (p< 0.05) and noxa (p<0.05) with a decrease in...
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Posted by admin on Sep 30, 2017 in |
An Accurate, sensitive, precise and stability indicating high performance thin layer chromatographic (HPTLC) method has been developed and validated for the estimation of SITA-P. The method was developed using TLC aluminium plates precoated with silica gel 60F254 as the stationary phase using ethyl acetate: methanol: formic acid (8.5:1:0.5 v/v/v) as mobile phase. Densitometric analysis of SITA-P was carried out in the absorbance mode at 265 nm. The retention factor for SITA-P was found to be 0.50 ± 0.04. Linearity was found to be 500 – 2500 ng/band for SITA-P. The method was found to be accurate, precise, and robust according to acceptance criteria. The limit of detection (LOD) and (LOQ) was found to be 124.36 ng/band and 376.87 ng/band for SITA-P respectively. The drug was subjected to stress condition. The method was validated for different parameters as per the International Conference for Harmonization guidelines (ICH). This HPTLC method can be used for the determination for the stability indicating assay methods for bulk drug and its...
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Posted by admin on Sep 30, 2017 in |
The study was to evaluate the hepatoprotective activity of aqueous extract of Pyrus pashia Buch.-Ham. ex D. Don against carbon tetrachloride-induced hepatotoxicity in mice. Hepatotoxicity was induced by CCl4 30% in olive oil (1ml/kg i.p.). Mice were treated with aqueous extract of P. pashia at doses of 250 and 500 mg/kg b.wt. orally for 14 days. There were two group pre-treatment (once daily for 14 days before CCl4 intoxication) and post-treatment (2, 6, 24 and 48 hr after CCl4 intoxication) groups. The observed effects were compared with a known hepatoprotective agent, silymarin. Pre-treatment and post-treatment groups of aqueous extract of P. pashia significantly reduced elevated serum levels of serum transaminases, alkaline phosphatase, and bilirubin and increased the level of total protein as compared to CCl4 treated group. The histopathological study also confirms the hepatoprotection. Preliminary qualitative phytochemical analysis of the plant revealed the presence of carbohydrates, phenolic compounds, tannins, and saponins. The data are expressed as ± S.E.M. one-way analysis of variance (ANOVA) followed by multiple comparisons with the...
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