Reactions catalyzed interfaces commonly occur at high coverage and in condensed media, causing turnover rates to depend on composition, collectively referred to as solvent effects. In a patent，Which mentioned a new discovery about Recommanded Product: 2,3-Dihydrobenzo[b][1,4]dioxin-6-amine, Recommanded Product: 2,3-Dihydrobenzo[b][1,4]dioxin-6-amine
Design and synthesis of small molecular dual inhibitor of falcipain-2 and dihydrofolate reductase as antimalarial agent
Resistance of malaria parasites has quickly developed to almost all used antimalarial drugs. Accordingly, the discovery of new effective drugs to counter the spread of malaria parasites that are resistant to existing agents, especially acting on multi-targets, is an urgent need. The cysteine protease falcipain-2 (FP-2) and dihydrofolate reductase (DHFR) play crucial roles in the Plasmodium life cycle. In this study, a series of first-gereration small molecular dual inhibitor of FP-2 and DHFR have been designed and synthesized based on the lead compound 1, which was randomly identified by screening FP-2 inhibitors in our laboratory. Six compounds (2f-g, 2j, and 2m-o) showed improved dual inhibitory activities against FP-2 (IC50 = 2.7-13.2 muM) and DHFR (IC50 = 1.8-19.8 muM), and the inhibitory capability of compound 2o against FP-2 and DHFR were increased ?8 and ?6 times than that of compound 1, respectively. Moreover, compound 2o exhibited moderate in vivo antimalarial activity in a dose dependent fashion, its safety and survival rate were slightly better than that of positive drug. The preliminary SAR was obtained, meanwhile, molecular modeling result provided the key structural information to maintain the dual inhibitory activity, and was helpful for future dual inhibitors design.
Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data. Recommanded Product: 2,3-Dihydrobenzo[b][1,4]dioxin-6-amine, If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 22013-33-8, in my other articles.