Anti-nociceptive and Anti-inflammatory Activity of Synthesized Novel Benzoxazole Derivatives.

INTRODUCTION: Pain is an immunological response to an infection or inflammation and long-term use of pain management therapy includes the use of Nonsteroidal anti-inflammatory drugs, which is associated with the occurrence of toxicity as well as gastrointestinal bleeding. Therefore, the investigation of new analgesic and anti-inflammatory agents remains a major challenge. AIMS: The objective of this research study is to undergo the pharmacological evaluation of newly synthesized benzoxazole derivatives. These novel derivatives were evaluated for anti-nociceptive, anti-inflammatory and cytotoxic activity using various in-vivo and ex-vivo methods Methods: The study was carried out using swiss mice (adult male) weighing between 20gm to 30gm and were divided into groups containing (n=6) six animals in each group for treatment. The anti-nociceptive activity was performed by using 0.1ml of 0.6% v/v acetic acid as nociception inducer and evaluated by the diminished number of abdominal writhes. The anti-inflammatory activity was done using 0.1 ml of 2% w/v Carrageenan induced paw edema method was observed which was evaluated by calculating the percent maximum possible effect. Histopathological evaluation and cytotoxic activity of the compounds were carried out. RESULTS: The results of this research study revealed that synthesized derivatives (a, b, c, d and e) showed promising anti-nociceptive and anti-inflammatory effects along significantly higher cytotoxic activity in MCF-7 cell lines. CONCLUSION: It can be concluded that synthesized derivatives (a, b, c, d and e) have potential anti- nociceptive and anti-inflammatory effects along with cytotoxic activity and certain modification in structure may result in the potent activity.

Synthesis and antimycobacterial activity of azetidine-, quinazoline-, and triazolo-thiadiazole-containing pyrazines.

The re-emergence of tuberculosis (TB) as a global health problem over the past few decades, accompanied by the rise of drug-resistant strains of Mycobacterium tuberculosis, emphasizes the need for the discovery of new therapeutic drugs against this disease. The emerging serious problem both in terms of TB control and clinical management prompted us to synthesize a novel series of N-[2-(substituted aryl)-3-chloro-4-oxoazetidin-1-yl]-2-(pyrazin-2-yloxy)acetamide, 6-(substituted aryl)-3-[(pyrazin-2-yloxy)methyl][1,2,4]triazolo[3,4-b][1,3,4]thiadiazole, and N-[6-({2-[(pyrazin-2-yloxy)acetyl] hydrazino}sulfonyl)-2-methyl-4-oxo-1,4-dihydroquinazolin-3(2H)yl]-substituted aryl sulfonamides. The compounds were synthesized using the appropriate synthetic route. All synthesized compounds were assayed in vitro for antimycobacterial activity against the H37 Rv strain of Mycobacterium tuberculosis. The minimum inhibitory concentration (MIC) was determined for the test compounds as well as for the reference standards. The compound which exhibited good antimycobacterial activity contains the substituents fluorine and methoxy. These electron-withdrawing or -donating substituents amend the lipophilicity of the test compounds which, in turn, alter the permeability across the bacterial cell membrane. Compounds 28, 37, and 43 showed good antimycobacterial activity while compound 51 showed a promising antimycobacterial activity.

Preparation and characterization of gliclazide-polyethylene glycol 4000 solid dispersions.

The objective of the present investigation was to study the effect of polyethylene glycol 4000 (PEG 4000) on in vitro dissolution of gliclazide from solid dispersions. Initial studies were carried out using physical mixtures of the drug and carrier. Solid dispersions were prepared by the melting or fusion method.Phase and saturation solubility study, in vitro dissolution of pure drug, physical mixtures and solid dispersions were carried out. PEG was found to be effective in increasing the dissolution of gliclazide in solid dispersions when compared to pure drug. FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug in the physical mixtures and solid dispersions. Dissolution enhancement was attributed to decreased crystallinity of the drug and to the wetting and solubilizing effect of the carrier from the solid dispersions of gliclazide. In conclusion, dissolution of gliclazide can be enhanced by the use of hydrophilic carrier.

Ketoprofen-loaded Eudragit RSPO microspheres: an influence of sodium carbonate on in vitro drug release and surface topology.

Eudragit RSPO microspheres containing ketoprofen as model drug, prepared by solvent evaporation technique using acetone-liquid paraffin (heavy) solvent system were examined. Depending upon polymer concentration in the internal phase, microspheres of particle mean diameter (122.8, 213.6 and 309.5 µm) were obtained. The influence of surface washing of microspheres with n-hexane, i.e. untreated microspheres (UM) on the drug content, drug release and surface topology of microspheres were compared to those of microspheres washed with sodium carbonate, i.e. treated microspheres (TM) in order to make the non-encapsulated surface drug soluble. The significant reduction in encapsulation efficiency (p < 0.001) and drug content (p < 0.001) after treatment, in combination with the small crystalline peaks observed during XRD testing and lack of melting endotherm observed in DSC testing, suggests that the washing process actually removes a significant amount of drug (p < 0.001) from the surface and encapsulated near to the surface of the microsphere polymer matrix. Scanning electron microscopy (SEM) examination revealed that the removal of surface drug did not affect the size of microspheres but the topology of treated smallest microspheres was modified. The ketoprofen release profiles were examined in phosphate buffer pH 7.4, using USPXXIII paddle type dissolution apparatus. In general both UM and TM result in biphasic release patterns, but the initial burst effect (first release phase) of TM was lower than that of UM. The second release phase did not change for the bigger size but increased for the smallest microspheres, probably owing to the modification of matrix porosity.

Antidiabetic activity of hydro-ethanolic extract of Cyperus rotundus in alloxan induced diabetes in rats.

In light of the traditional claim of Cyperus rotundus in the treatment of diabetes, investigations were carried out to evaluate its effect on alloxan induced hyperglycemia in rats. Oral daily administration of 500 mg/kg of the extract (once a day for seven consecutive days) significantly lowered the blood glucose levels. This antihyperglycemic activity can be attributed to its antioxidant activity as it showed the strong DPPH radical scavenging action in vitro.

Synthesis and preliminary evaluation of some pyrazine containing thiazolines and thiazolidinones as antimicrobial agents.

A series of N'-[3,4-disubstituted-1,3-thiazol-2(3H)-ylidene]-2-(pyrazin-2-yloxy)acetohydrazide 11-66 and N'-[(2Z)-3-(4-bromophenyl)-4-oxo-1,3-thiazolidin-2-ylidene]-2-(pyrazin-2-yloxy)acetohydrazide 68-74 were synthesized using appropriate synthetic route. The entire test compounds 11-66 and 68-74 were assayed in vitro for antibacterial activity against two different strains of Gram-negative (E. coli and S. typhi), Gram-positive (S. aureus and B. subtilis) bacteria and the antimycobacterial activity was evaluated against H(37)Rv strain of Mycobacterium tuberculosis. The minimum inhibitory concentration (MIC) was determined for test compounds and for reference standards. The test compounds showed significant antibacterial and antimycobacterial activity against the microbial strains used, when tested in vitro. In general, pyrazine ring and substituted thiazoline ring are essential for antimicrobial activity. Among the compounds tested, compounds 11, 12 and 40 were found to be most potent. The toxicity of most potent compounds 11, 12 and 40 were determined using hemolytic assay and minimal hemolytic concentration (MHCs) were determined. The test compounds were found to be nontoxic up to a dose level of 250 microg/mL.