Project description:Cudrania tricuspidata extracts and 3 major compounds, including 4'-O-Methylalpinumisoflavone, Alpinumisoflavone and 6,8-diprenylgenistein
Project description:Andrographis paniculata Nees and its major compound andrographolide is known to exhibit a pleothera of activities. Active component enriched extracts are known to provide various beneficial effects, and therefore it was interesting to investigate whether increased amount of major compound alters gene expression. To acheive this, HePG2 cells treated with Andrographis paniculata extract (AP) and andrographolide enriched –extract (AP20) were subjected to microarray analysis to check their effect on global gene expression.
Project description:Use CEN quechers method to extract 2.5g honey and use PSA to clean up matrix. Using ACN-water-0.01%HCOOH for compound separation and HRMS analysis with Thermo Orbitrap Exploris 120. Data was acquired in Full scan-ddms2 mode. This included a full scan over the m/z range 100- 1000 at full width at half maximum (FWHM) resolution of 60,000, and a data-dependent-MS2 scan at FWHM resolution of 15,000 on the top 4 ions. The ionization was performed in positive ESI with an inlusion list collated from OPPIN website, and to gain more information about fragment ions in the QC sample, we use an Automated Exclusion List Generation workflow, so one QC sample finally gave 3 injections.
Project description:Glioblastoma is the most common and malignant primary brain tumor in adults with current treatment presenting limited effectiveness. Resistance to therapy is consequence of the high molecular and cellular heterogeneity. Multitarget small molecules (MSMs) are emerging as a novel therapeutic strategy for the treatment of complex diseases, including cancer. In the present work, we have generated a novel family of indole-based MSMs designed to inhibit monoamine oxidases (MAOs), cholinesterases (ChEs) and histone deacetylases (HDACs), while acting as histamine H3 receptor (H3R) antagonists and sigma 1 receptor (S1R) agonists. For this, selected pharmacophoric moieties of the parent compounds Contilisant and Belinostat HDAC inhibitor were juxtaposed. 9 MSMs were synthesized and most of them exerted cytotoxic effect on glioma cells. Among them, 3 molecules were selected (MTP142, MTP156 and MTP150), and additional experiments revealed that they inhibited glioma stem cell (GSCs) activity, did not present toxicity and are expected to cross the BBB. In vivo and Omic studies were performed with MTP150 molecule and results showed that it significantly reduced tumor growth in vivo, both alone and in combination with temozolomide (TMZ). Finally, transcriptomic and proteomic analyses on patient-derived GSCs revealed a deregulation in cell cycle and neurotransmission activity by the treatment with MTP150. In conclusion, our data reveal the efficacy of a novel family of MSMs in the pre-clinical setting of glioblastoma.
Project description:Gene expression profiling of Mycobacterium tuberculosis H37Rv in response to compound CDRI-5g (Saquib, M. et al. Eur. J. Med. Chem. 46 (2011) 2217-2223) was studied by administration of compound at 10 µg/ml in broth culture. RNA was extracted at two time points 12 h and 24 h of growth from replicating phase and compound added culture. Replicating phase culture was incubated for the same time and used as a control. Experiment was repeated three times and for each time points triplicate culture was pelleted to isolate total RNA using Qiagen RNA isolation kit.