《Imidazo[2,1-b] [1,3,4]thiadiazoles with antiproliferative activity against primary and gemcitabine-resistant pancreatic cancer cells》 was published in European Journal of Medicinal Chemistry in 2020. These research results belong to Cascioferro, Stella; Li Petri, Giovanna; Parrino, Barbara; Carbone, Daniela; Funel, Niccola; Bergonzini, Cecilia; Mantini, Giulia; Dekker, Henk; Geerke, Daan; Peters, Godefridus J.; Cirrincione, Girolamo; Giovannetti, Elisa; Diana, Patrizia. Safety of 5-Fluoro-1H-indole The article mentions the following:
A new series of eighteen HBr salts or free bases of imidazo[2,1-b][1,3,4]thiadiazoles I [R = H, MeO, Cl, F, Br; R1 = H, Me; R2 = Ph, 3-thienyl, 4-fluorophenyl, etc.; R3 = H, CHO] were efficiently synthesized and screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. Two out of eighteen derivatives, HBr salt of compounds I [R = R1 = R3 = H, R2 = 3-thienyl; R = F, R1 = Me, R2 = 3-thienyl, R3 = H] showed remarkably cytotoxic activity with the half maximal inhibitory concentration values (IC50) ranging from 0.23 to 11.4μM, and 0.29-12.2μM, resp. However, two addnl. compounds, I [R = R3 = H, R1 = Me, R2 = 3-thienyl, HBr salt; R = F, R1 = R3 = H, R2 = 3-thienyl] displayed remarkable in-vitro antiproliferative activity against pancreatic ductal adenocarcinoma (PDAC) cell lines, including immortalized (SUIT-2, Capan-1, Panc-1), primary (PDAC-3) and gemcitabine-resistant (Panc-1R), eliciting IC50 values ranging from micromolar to sub-micromolar level, associated with significant reduction of cell-migration and spheroid shrinkage. These remarkable results were explained by modulation of key regulators of epithelial-to-mesenchymal transition (EMT), including E-cadherin and vimentin, and inhibition of metalloproteinase-2/-9. High-throughput arrays revealed a significant inhibition of the phosphorylation of 45 tyrosine kinases substrates, whose visualization on Cytoscape highlighted PTK2/FAK as an important hub. Inhibition of phosphorylation of PTK2/FAK was validated as one of the possible mechanisms of action, using a specific ELISA. In conclusion, novel imidazothiadiazoles show potent antiproliferative activity, mediated by modulation of EMT and PTK2/FAK. In the experimental materials used by the author, we found 5-Fluoro-1H-indole(cas: 399-52-0Safety of 5-Fluoro-1H-indole)
5-Fluoro-1H-indole(cas: 399-52-0) is a member of aromaticfluorinated building blocks. Fluorine-containing aromatics have been incorporated into crop-protection chemicals (herbicides, insecticides, fungicides). Liquid crystals, positron emission tomography, and imaging systems represent new areas where fluoroaromatics and fluoroheterocyclics have gained attention.Safety of 5-Fluoro-1H-indole
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Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles