Synthesis, Characterization and Evaluation of Analgesic and Anti-inflammatory Activities of Some Novel Indoles

Purpose: Long-term clinical usage of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant side effects - gastrointestinal lesions, bleeding and nephrotoxicity. Therefore, the discovery of new safer antiinflammatory drugs represents a challenging goal for this research area.Methods: Various derivatives of 3-(2-aminopyrimidin-4-yl) indoles viz. 4-(4-substitutedphenyl)-6-(2-(4-substitutedphenyl)-1H-indol-3-yl) pyrimidin-2-amine (4a-4r) were synthesized by cyclization of (3-(4- substitutedphenyl)-1-(2-(4-substitutedphenyl)-1H-indol-3-yl) prop-2-en-1-one) of indole with guanidine hydrochloride in the presence of sodium isopropoxide. Their structures were confirmed by FTIR, 1H NMR and elemental analysis. These compounds were investigated for their analgesic, inflammatory and ulcerogenic activities.Results: All the compounds tested (4a-4r) showed analgesic and inflammatory activities. Seven compounds (4d, e, h, j, k, q, p) out of 18 compounds showed antiinflammatory activity comparable to that of the reference standard, indomethacin, but with much lower ulcerogenic action. Compounds 4j and 4k showed 87.4 and 88.2 % inhibition of paw edema, 78.5 and 76.6 % protection against acetic acid-induced writhings and 0.89 and 1.12 of severity index, respectively, compared to 92.7 %, 82.8 %and 2.2, respectively, for indomethacin.Conclusion: The results show that incorporation of an appropriately substituted pyrimidine ring in indole nucleus can afford molecules with good analgesic and anti-inflammatory activities but with reduced gastric irritation.Keywords: Synthesis, Indole, Pyrimidine, Anti-inflammatory activity, Analgesic activity, Ulcerogenic effec

Quantitative Proteomics Reveals the Dynamic Protein Landscape during Initiation of Human Th17 Cell Polarization

Th17 cells contribute to the pathogenesis of inflammatory and autoimmune diseases and cancer. To reveal the Th17 cell-specific proteomic signature regulating Th17 cell differentiation and function in humans, we used a label-free mass spectrometry-based approach. Furthermore, a comprehensive analysis of the proteome and transcriptome of cells during human Th17 differentiation revealed a high degree of overlap between the datasets. However, when compared with corresponding published mouse data, we found very limited overlap between the proteins differentially regulated in response to Th17 differentiation. Validations were made for a panel of selected proteins with known and unknown functions. Finally, using RNA interference, we showed that SATB1 negatively regulates human Th17 cell differentiation. Overall, the current study illustrates a comprehensive picture of the global protein landscape during early human Th17 cell differentiation. Poor overlap with mouse data underlines the importance of human studies for translational research

Case Report - Giant Cell Tumour of Talar Body

Giant cell tumour (osteoclastoma) of talar bone is a rare entity and is seen more commonly in the third decade of life. We report this disease entity in a 17-year-old girl. The patient presented with painful swelling of the left ankle with an osteolytic lesion in the talus on conventional radiographs. Intralesional curettage and autologous bone grafting was performed following which patient's pain and swelling disappeared. Complete range of movement at the ankle joint was regained with minimal restriction at the subtalar joint. There is no evidence of relapse at six months follow up