Hybrid Computational Simulation and Modeling Assisted Structural Analysis of Anti-tubercular Molecules

AbstractTuberculosis (TB), a leading cause of death worldwide, in association with HIV-AIDS and the emergence of multi-drug resistance (MDR) or extensively drug resistance (XDR) strains, has created necessity to develop new class of anti-tubercular drug. Strategic implementation of hybrid computational simulation and searching method has been used to analyze and explore new chemical entity effective against MDR Tuberculosis strains. Initially a ligand-based pharmacophore hypothesis and 3D Quantitative structure activity relationship (QSAR) model with statistical significance (R2=0.985, SD=0.146, Pearson R=0.936, Q2= 0.849, R2Pred=0.851, Q2(F2)=0.854) was generated by well validated algorithm. Concurrently molecular docking analysis was performed by considering three individual grid points of InhA enzyme. Moreover Ligand-based pharmacophoric model was drastically re-assessed against receptor-based docking simulation model to authenticate this in silico trialing. The docking analysis indicates that this class of ligands nicely occupies the hydrophobic pocket of InhA enzyme, which is an important feature of direct InhA inhibitors and it reveals that the chemical entities can inhibit the aforementioned enzyme without activating katG (a catalase/peroxidase enzyme) enzyme pathway

Development and Evaluation of Controlled Release Bilayer Tablets of Hydrochlorothiazide and Losartan Potassium

The aim of the present research work was to develop bilayer tablet dosage form containing combination of immediate and sustained matrix prepared from Hydrochlorothiazide (HTZ) and Losartan Potassium (LP) respectively for the treatment of hypertension and its associated complications. Immediate release HTZ was prepared using different superdisintegrants. LP sustained layer was prepared by compression technique. Both pre-compression and post-compression parameters were analyzed for all the tablets. In vitro release studies were carried out as per USP in pH (1.2) and phosphate buffer pH (6.8) using USP-XXI type II. Bilayer tablet (F6) formulated using higher concentration of HPMC K 15 exhibiting higher LP release rate (83.553± 0.22) for the period of 12 h. The In vitrorelease profile of drug from sustained matrix could be best expressed by First order as the plot showed highest linearity (R2 = 0.990) and diffusion was the dominating mechanism of drug release. The stability and FTIR studies are also indicating the absence of strong interaction between drug and polymer and compatibility among them

Development and Evaluation of Controlled Release Bilayer Tablets of Hydrochlorothiazide and Losartan Potassium

The aim of the present research work was to develop bilayer tablet dosage form containing combination of immediate and sustained matrix prepared from Hydrochlorothiazide (HTZ) and Losartan Potassium (LP) respectively for the treatment of hypertension and its associated complications. Immediate release HTZ was prepared using different superdisintegrants. LP sustained layer was prepared by compression technique. Both pre-compression and post-compression parameters were analyzed for all the tablets. In vitro release studies were carried out as per USP in pH (1.2) and phosphate buffer pH (6.8) using USP-XXI type II. Bilayer tablet (F6) formulated using higher concentration of HPMC K 15 exhibiting higher LP release rate (83.553± 0.22) for the period of 12 h. The In vitrorelease profile of drug from sustained matrix could be best expressed by First order as the plot showed highest linearity (R2 = 0.990) and diffusion was the dominating mechanism of drug release. The stability and FTIR studies are also indicating the absence of strong interaction between drug and polymer and compatibility among them

Preliminary screening of Waltheria indica (L.) plant for its anti-inflammatory activity

The investigation on anti-inflammatory activity of the various extract of Waltheria indica L. was reported to find out the pharmacological basis for its ethnomedical use. The anti-inflammatory activity of the pet ether (PEW) and methanol (MEW) extracts of the leaves of Waltheria indica L. (Malvaceae)were evaluated by using in vivo (Carrageenan & histamine induced rat paw edema, cotton pellet granuloma test) models. It was observed that, all the extracts showed significant activity in the in-vivo model at the dose of 500 mg/kg b.w. orally, when compared with control and standard drugs. Of the two extracts tested, methanol extract MEW showed most significant activity well in comparison to the standard drug.  Therefore, present study suggests, potential of leaves of Waltheria indica L. in both models of acute and chronic inflammation.

Evaluation of hepatoprotective effect of Waltheria indica against various NSAIDs-induced hepatic damage in rats

The objective of the present study was to evaluate methanolic extract of leaves of Waltheria indica linn. for hepatoprotective potency of the potent solvent extract. The hepatotoxicity was induced by diclofenac, carbon tetrachloride (CCl 4 ) and acetaminophen. In CCl 4 induced hepatotoxicity study, animals were divided into five groups (n=6). Methanolic extract of Waltheria indica (WIM) groups were injected in doses of 400 mg/kg and 600mg/kg body weight along with CCl 4 and Silymarin 100mg/kg was taken as standard drug. Similarly procedure was followed in diclofenac and acetaminophen induced hepatotoxicity. Blood samples and liver were collected and liver hisopathological studies were carried out. These histopathological analysis suggested that WIM extract have the ability to reduce the degree of hepatic fibrosis induced by various factors. And concluded that WIM extract has significant hepatoprotective activity thus this study scientifically support the theory to use of this plant in traditional medicine for the treatment of liver disorders