Sudha

Anxiety disorders are marked by excessive fear, often in response to specific objects or situations and in the absence of true danger and they are extremely common in the general population. According to a recent epidemiological study, the lifetime prevalence of any anxiety disorder is 28.8%. Anxiety disorders are associated with impaired workplace performance and hefty economic costs. The clinical applications of benzodiazepines as anxiolytic are limited by their side effects. The aim of the present study is to investigate the effects of aqueous and ethanolic extracts of Solanum Nigrum leaves.  Elevated plus maze test, light/dark test used. In the elevated plus maze, aqueous and ethanolic extracts (400mg/kg; p.o) showed an anxiolytic effect by increasing the percentage of time spent in open arms and the percentage of open arm entries as compared to control group.. In the light/dark transition test, aqueous extracts (400mg/kg; p.o) had increased the time spent in light area, latency to enter dark chamber and tunnel crossing. Whereas, ethanolic extract of (400mg/kg; p.o) has showed significant result. These results suggested that the extracts of Solanum Nigrum leaves possessed anxiolytic effect in mice, in contrast to diazepam, had no inhibitory effect on locomotion in these tests, its side effect profile might be superior to the benzodiazepines.

The poor aqueous solubility of Glimepiride is the major factor limiting its oral bioavailability.  The objective of the work is to enhance the solubility of Glimepiride, there by its bioavailability by using solid dispersion technique. Solid dispersions of Glimepiride were prepared by using Poly vinyl Pyrrolidone (PVP K30), by solvent evaporation method in different ratios of 1:0.5, 1:1, 1:3, 1:5 respectively and evaluated for its in vitro & in vivo release along with Mdsc & FTIR. The equilibrium solubility of solid dispersions was determined in water to study the effect of PVP K30 on solubility of Glimepiride. In Vitro dissolution studies were conducted in water from solid dispersions equivalent to 4 mg of Glimepiride. Protocol bound in vivo studies were conducted in non diabetic rats with the best formulation. Two groups of rats (6 rats in each group) were orally fed Glimepiride as plain drug dispersion (control group) & as drug: PVP K30 solid dispersion (test group). The fall in blood glucose level was monitored over 24 hours. Successful conversion of the crystalline Glimepiride to amorphous solid dispersion was achieved at 1:5 level of drug to PVP K30 (F4). The solid dispersion prepared with PVP K30 at 1:5 level (F4) showed a 4 folds enhancement in aqueous solubility of the drug. So the in vivo studies conducted with 1:5 drug to PVP K30 (F4) solid dispersion, the best formulation, it was observed that the fall in the test group is significantly faster and more intense as compared to the control group. The above study shows that solid dispersion of Glimepiride offers an simple and attractive solution to increase the solubility of the poorly water soluble drug and thereby improve its oral bioavailability. Key words: Glimepiride, Poly vinyl Pyrrolidone (PVP K30), Solid dispersions (SD)

The aim of the present study is to minimize the local gastrointestinal irritation which is one of the major side effects of Piroxicam (PR) by the formulation  oral  stomach specific in situ gelling emulsion ingestion by kinetic control of drug release. Material and method: In situ emulgel were prepared by using castor oil as oil phase ,tween 80 and span 80 as emulsifiers, sodium alginate was used as gelling agent,  xanthan gum was used as release retardant ,calcium carbonate was used as cross linking agent, pH triggered ionic gelation is the mechanism involved in the present study. Various evaluation tests were done for all formulations Results: Formulation F9 containing 2.5% of sodium alginate, 2 % of CaCO3, 1 % of sodium bicarbonate and 0.8% of Xanthan gum was selected as optimized batch based on  Q10 86.02±0.17 %, floating time 122.15±2.47 sec and drug content 91.86±1.02 %. The release pattern of drug was found to follow Korsemeyer and Highuchi model. The DSC study exposed that there was no incompatibility. Pharmacodynamic study on Wistar rats were showed significant anti inflammatory and anti arthritic activity of the optimized formulation. Further, in vivo toxicity studies carried out in wistar rats revealed no signs of gastric ulceration upon prolonged dosing. Conclusion: It was concluded that the oral stomach specific In situ gelling emulsion of piroxicam could be an effective dosage form which minimize the gastric irritation by coating drug with castor oil and remains buoyant and control the drug release for 24hrs.

Buccal administration of drugs provides a convenient route of administration for both systemic and local drug actions. However, the preferred site for retentive oral transmucosal delivery systems and for sustained- and controlled-release delivery devices is the buccal mucosa, mainly because of the differences in permeability characteristics between the two regions and the buccal mucosa’s expanse of smooth and relatively immobile mucosa. The buccal mucosa offers excellent possibilities for the (long-term) delivery of suitable drugs, especially for metabolically unstable drugs, such as peptides. In the development of these buccal drug delivery systems, mucoadhesion of the device is a key element. Mucoadhesive polymers have been utilized in many different dosage forms in efforts to achieve systemic delivery of drugs through the buccal mucosa. Buccoadhesive drug delivery is relatively new drug delivery strategy; in this traditional polymers are replaced by novel bioadhesive polymers such as thiomers & lectins etc. to overcome limitation of traditional polymer.

An effective and economical protocol was developed for the synthesis of 3-substituted indoles by one-pot three-component coupling reaction of a substituted salicylaldehyde, N-methylaniline and indole using [Hmim] HSO4 as a catalyst. All the synthesized derivatives were evaluated for inhibition of cancer cell. The initial assays indicated that some of the newly synthesized compounds displayed significantly good inhibition activities against human breast cancer cell (MCF7), cell lines compared with the control (Adriamysin), which might be developed as novel lead scaffold for potential anticancer agents.

This research has focused on the incorporation of the thiadiazole moiety into versatile pyridine ring because of their biological properties. In order to explore the possibilities of some altered biological action author envisaged that by designing the Schiff base derivatives of 1, 3, 4-thiadiazole moiety may exhibit anticancer properties. These novel 1,3,4-thiadiazole Schiff base compounds have been synthesized by microwave-assisted synthesis and screened for their cytotoxicity on HeLa, HepG2 and MCF7 cancer cell lines.The key intermediate 2-(4-fluorophenyl)pyridine-3-carboxylic acid was obtained by hydrolysing the ester 3 in presence of KOH and methanol.Thus obtained compound 4 was treated with thiosemicarbazide and phosphorous oxychloride and cyclized in microwave inorder to get the intermediate 5-[2-(4-fluorophenyl) pyridin-3-yl]-1, 3, 4-thiadiazol-2-amine. The amine 5 was reacted with different aldehydes (a-h) in presence of catalytic amount of acetic acid and obtaineda series of novel Schiff base derivatives 6a-6h. These compounds were characterized by MS, 1H-NMR,IR and elemental analysis. Most of the compounds in this series have exhibited moderate cytotoxicity onall the three human cell lines at different concentrations, but two compounds 6f and 6h showed good inhibition towards liver carcinoma cell lines having IC50 of 23.8µMand 13.4µM respectively.

In the present study a series of 20 histone deacetylase 8 (HDAC8) inhibitors were used for generation of pharmacophore. A five features pharmacophore with one hydrogen bond acceptor (A), two hydrogen bond donors (DD) and two ring aromatics (RR) was developed and used for searching compound database. A statistically significant atom based 3D QSAR model was built by selecting best pharmacophore hypothesis ADDRR.3 with R2 = 0.9821 for training set of 14 molecules and Q2= 0.7314, RMSE= 0.1709, Person-R= 0.9061 for test set of 6 molecules. These parameters indicate that the model is a good predictive model. Docking study of known inhibitors as well as hits resulted after data base searching having fitness score ≥ 1 was performed. Docking analysis shows the important residues in the active site of receptor are Zn-388, TYR-306, HIS-142, PHE-152, PHE-208, GLY-151, and HIE-180. The XP glide score of highest active compound 1 and lowest active 20 are -11.73 and -6.036 respectively, which corroborated with experimental activity. On the basis of pharmacophore matching, predicted activity and docking interactions 5 novel chemical scaffold (Code No: CACPD2011a-0001275680, CACPD2011a-0000573705, CACPD2011a-0001843791, CACPD2011a-0000300107, CACPD2011a-0000291783) are reported as potent HDAC8 inhibitors.

In the present study structure based virtual screening of compound data base, prediction of activity of high extra precision glide docking scored (XPGS) molecules by atom based 3D QSAR model, XP glide docking analysis of known inhibitors to know the key residue interactions and ADME study of identified Histone Deacetylase 2 (HDAC2) inhibitors were performed. A 3D QSAR model was build for both training set (R2 = 0.9867, SD= 0.104, F= 322.1 and N= 17) and test set (Q2 = 0.9137, Pearson r= 0.9671, RMSE = 0.160, N = 7) molecules and showed a statistically significant and good predictive model. The visualization of 3D QSAR model suggested that introduction of hydrogen bond donor group in 5-position of pyridine ring, 6-position of 1,2-diaminobenzene ring; hydrophobic groups in the 2,4-position of pyridine ring, 5,6 -position of 1,2-diamino benzene ring, 2,3,5,6-position of amonomethylbenzamide ring of highest active compound 1 were suitable to increase the HDAC2 inhibitory activity. The XP glide docking analysis of the known inhibitors showed that residues PHE-155, Gly-154, His-145, His-146, Asp-104 and Zn-ligand interaction in the active site region play a crucial role for inhibitory activity. The activity of high glide scored molecules resulted from virtual screening were predicted by atom based 3D QSAR model. After prediction of activity the molecules were subjected to ADME study to know the drug likeness properties and reported 10 molecules having XPGS > 12.0 and predicted activity > 6.7 as potent HDAC2 inhibitors. The docking interaction of known inhibitors was also similar to the docking interaction of identified ten potent inhibitors.

Garcinia pedunculata is a medicinal plant commonly known as Amlavetasa, belonging to the family Clusiaceae. The fruit of Garcinia pedunculata were used in the diet as a spice. It has been used as folk remedy in different ailments such as chronic catarrh, asthma, cough, bronchitis, cardiotonicand fever. The present study has been carried out to evaluate the anti inflammatory activity of aqueous extract of fruits of Garcinea pedunculata by carrageenan induced paw edema method. Eighteen healthy wistar albino rats were divided into three different groups of six rats each. Group I administered with normal tap water (5ml/kg) served as normal control. Group II administered with Ibuprofen 100mg/kg served as reference standard and group III administered with aqueous extract of fruits of Garcinea pedunculata(400mg/kg). In Acute oral toxicity study there was no mortality in any dose up to 2000mg/kg. The aqueous extract of fruits of Garcinea pedunculata has shown significant anti inflammatory activity by significantly decrease in the paw volume recorded at three different time interval compared with control group (**p< 0.01). It can be concluded that aqueous extract of fruits of Garcinea pedunculatahas potent anti inflammatory activity and there is a need for further scientific investigation to explore its anti inflammatory activity.

This study was performed to evaluate the In vitro antimicrobial activity of entire parts of aqueous and methanolic extracts of Sphaeranthus amaranthoides Burm. The antimicrobial activities of medicinal plant extracts used for the treatment of parasitic diseases were examined with four bacteria – two from Gram positive group (Bacillus subtilis and Staphylococcus aureus) and rest two from Gram-negative group (Escherichia coli and Salmonella typhi) following disc diffusion method. The methanolic extract revealed antibacterial activity more than the aqueous extract. Both the extracts showed less activity against Bacillus subtilis and where as Salmonella typhi no inhibition (NI). It showed more activity on Escherichia coli compared to standard. Both the extracts showed minimum inhibitory concentration (MIC) of 25mg/ml on Bacillus subtilis and 12.5mg/ml on Staphylococcus aureus. Totally the methanolic and aqueous extracts of Sphaeranthus amaranthoids showed good anti bacterial activity. Phytochemical screening revealed the presence of steroids, alkaloids, sugars, phenolics, flavonoids, saponins, tannins and amino acids with mottled degree