779335-05-6Relevant articles and documents
Inhibitors of plasmodial serine hydroxymethyltransferase (SHMT): Cocrystal structures of pyrazolopyrans with potent blood- and liver-stage activities
Witschel, Matthias C.,Rottmann, Matthias,Schwab, Anatol,Leartsakulpanich, Ubolsree,Chitnumsub, Penchit,Seet, Michael,Tonazzi, Sandro,Schwertz, Geoffrey,Stelzer, Frank,Mietzner, Thomas,McNamara, Case,Thater, Frank,Freymond, Céline,Jaruwat, Aritsara,Pinthong, Chatchadaporn,Riangrungroj, Pinpunya,Oufir, Mouhssin,Hamburger, Matthias,M?ser, Pascal,Sanz-Alonso, Laura M.,Charman, Susan,Wittlin, Sergio,Yuthavong, Yongyuth,Chaiyen, Pimchai,Diederich, Fran?ois
, p. 3117 - 3130 (2015/04/27)
Several of the enzymes related to the folate cycle are well-known for their role as clinically validated antimalarial targets. Nevertheless for serine hydroxymethyltransferase (SHMT), one of the key enzymes of this cycle, efficient inhibitors have not been described so far. On the basis of plant SHMT inhibitors from an herbicide optimization program, highly potent inhibitors of Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) SHMT with a pyrazolopyran core structure were identified. Cocrystal structures of potent inhibitors with PvSHMT were solved at 2.6 ? resolution. These ligands showed activity (IC50/EC50 values) in the nanomolar range against purified PfSHMT, blood-stage Pf, and liver-stage P. berghei (Pb) cells and a high selectivity when assayed against mammalian cell lines. Pharmacokinetic limitations are the most plausible explanation for lack of significant activity of the inhibitors in the in vivo Pb mouse malaria model.
Live-cell-permeant thiophene fluorophores and cell-mediated formation of fluorescent fibrils
Palama, Ilaria,Di Maria, Francesca,Viola, Ilenia,Fabiano, Eduardo,Gigli, Giuseppe,Bettini, Cristian,Barbarella, Giovanna
supporting information; experimental part, p. 17777 - 17785 (2012/01/04)
In our search for thiophene fluorophores that can overcome the limits of currently available organic dyes in live-cell staining, we synthesized biocompatible dithienothiophene-S,S-dioxide derivatives (DTTOs) that were spontaneously taken up by live mouse embryonic fibroblasts and HeLa cells. Upon treatment with DTTOs, the cells secreted nanostructured fluorescent fibrils, while cell viability remained unaltered. Comparison with the behavior of other cell-permeant, newly synthesized thiophene fluorophores showed that the formation of fluorescent fibrils was peculiar to DTTO dyes. Laser scanning confocal microscopy of the fluorescent fibrils showed that most of them were characterized by helical supramolecular organization. Electrophoretic analysis and theoretical calculations suggested that the DTTOs were selectively recognized by the HyPro component of procollagen polypeptide chains and incorporated through the formation of multiple H-bondings.
Chemical Compounds
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Page/Page column 31, (2009/01/20)
There is provided a compound of Formula (I) or a salt, solvate, or physiologically functional derivative thereof:
