Dawidowski, Maciej; Kalel, Vishal C.; Napolitano, Valeria; Fino, Roberto; Schorpp, Kenji; Emmanouilidis, Leonidas; Lenhart, Dominik; Ostertag, Michael; Kaiser, Marcel; Kolonko, Marta; Tippler, Bettina; Schliebs, Wolfgang; Dubin, Grzegorz; Maeser, Pascal; Tetko, Igor V.; Hadian, Kamyar; Plettenburg, Oliver; Erdmann, Ralf; Sattler, Michael; Popowicz, Grzegorz M. published the artcile< Structure-Activity Relationship in Pyrazolo[4,3-c]pyridines, First Inhibitors of PEX14-PEX5 Protein-Protein Interaction with Trypanocidal Activity>, Safety of Methyl 1H-indole-7-carboxylate, the main research area is Trypanosoma infectious diseases PEX14 PEX5 PPI metabolic pathways MDS.
Trypanosoma protists are pathogens leading to a spectrum of devastating infectious diseases. The range of available chemotherapeutics against Trypanosoma is limited, and the existing therapies are partially ineffective and cause serious adverse effects. Formation of the PEX14-PEX5 complex is essential for protein import into the parasites’ glycosomes. This transport is critical for parasite metabolism and failure leads to mislocalization of glycosomal enzymes, with fatal consequences for the parasite. Hence, inhibiting the PEX14-PEX5 protein-protein interaction (PPI) is an attractive way to affect multiple metabolic pathways. Herein, we have used structure-guided computational screening and optimization to develop the first line of compounds that inhibit PEX14-PEX5 PPI. The optimization was driven by several X-ray structures, NMR binding data, and mol. dynamics simulations. Importantly, the developed compounds show significant cellular activity against Trypanosoma, including the human pathogen Trypanosoma brucei gambiense and Trypanosoma cruzi parasites.
Journal of Medicinal Chemistry published new progress about Chagas disease. 93247-78-0 belongs to class indole-building-block, and the molecular formula is C10H9NO2, Safety of Methyl 1H-indole-7-carboxylate.
Referemce:
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