Prions are misfolded proteins involved in neurodegenerative diseases of high interest in veterinary and public health. In this work, we report the chemical space exploration around the anti-prion compound BB 0300674 in order to gain an understanding of its Structure Activity Relationships (SARs). A series of 43 novel analogues, based on four different chemical clusters, were synthetized and tested against PrPSc and mutant PrP toxicity assays. From this biological screening, two compounds (59 and 65) emerged with a 10-fold improvement in anti-prion activity compared with the initial lead compound, presenting at the same time interesting cell viability.
Generation, optimization and characterization of novel anti-prion compounds / Altieri, A.; Spiridonov, E. A.; Sivtzev, S. I.; Ishibashi, D.; Biggi, S.; Nishida, N.; Biasini, E.; Kurkin, A. V.. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 28:21(2020), p. 115717. [10.1016/j.bmc.2020.115717]
Generation, optimization and characterization of novel anti-prion compounds
Biggi S.;Biasini E.;
2020-01-01
Abstract
Prions are misfolded proteins involved in neurodegenerative diseases of high interest in veterinary and public health. In this work, we report the chemical space exploration around the anti-prion compound BB 0300674 in order to gain an understanding of its Structure Activity Relationships (SARs). A series of 43 novel analogues, based on four different chemical clusters, were synthetized and tested against PrPSc and mutant PrP toxicity assays. From this biological screening, two compounds (59 and 65) emerged with a 10-fold improvement in anti-prion activity compared with the initial lead compound, presenting at the same time interesting cell viability.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione
