On February 25, 2021, Le Manach, Claire; Dam, Jean; Woodland, John G.; Kaur, Gurminder; Khonde, Lutete P.; Brunschwig, Christel; Njoroge, Mathew; Wicht, Kathryn J.; Horatscheck, Andre; Paquet, Tanya; Boyle, Grant A.; Gibhard, Liezl; Taylor, Dale; Lawrence, Nina; Yeo, Tomas; Mok, Sachel; Eastman, Richard T.; Dorjsuren, Dorjbal; Talley, Daniel C.; Guo, Hui; Simeonov, Anton; Reader, Janette; van der Watt, Mariette; Erlank, Erica; Venter, Nelius; Zawada, Jacek W.; Aswat, Ayesha; Nardini, Luisa; Coetzer, Theresa L.; Lauterbach, Sonja B.; Bezuidenhout, Belinda C.; Theron, Anjo; Mancama, Dalu; Koekemoer, Lizette L.; Birkholtz, Lyn-Marie; Wittlin, Sergio; Delves, Michael; Ottilie, Sabine; Winzeler, Elizabeth A.; von Geldern, Thomas W.; Smith, Dennis; Fidock, David A.; Street, Leslie J.; Basarab, Gregory S.; Duffy, James; Chibale, Kelly published an article.Electric Literature of 32462-30-9 The title of the article was Identification and Profiling of a Novel Diazaspiro[3.4]octane Chemical Series Active against Multiple Stages of the Human Malaria Parasite Plasmodium falciparum and Optimization Efforts. And the article contained the following:
A novel diazaspiro[3.4]octane series was identified from a Plasmodium falciparum whole-cell high-throughput screening campaign. Hits displayed activity against multiple stages of the parasite lifecycle, which together with a novel sp3-rich scaffold provided an attractive starting point for a hit-to-lead medicinal chem. optimization and biol. profiling program. Structure-activity-relationship studies led to the identification of compounds that showed low nanomolar asexual blood-stage activity (<50 nM) together with strong gametocyte sterilizing properties that translated to transmission-blocking activity in the standard membrane feeding assay. Mechanistic studies through resistance selection with one of the analogs followed by whole-genome sequencing implicated the P. falciparum cyclic amine resistance locus in the mode of resistance. The experimental process involved the reaction of H-Phg(4-OH)-OH(cas: 32462-30-9).Electric Literature of 32462-30-9
The Article related to malaria antimalarial plasmodium diazaspirooctane pharmacokinetic, Pharmacology: Effects Of Antimicrobials and Parasiticides and other aspects.Electric Literature of 32462-30-9
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