TY  - JOUR
AU  - Ruan, B
AU  - Zhang, Y
AU  - Tadesse, S
AU  - Preston, S
AU  - Taki, AC
AU  - Jabbar, A
AU  - Hofmann, A
AU  - Jiao, Y
AU  - Garcia-Bustos, J
AU  - Harjani, J
AU  - Le, TG
AU  - Varghese, S
AU  - Teguh, S
AU  - Xie, Y
AU  - Odiba, J
AU  - Hu, M
AU  - Gasser, RB
AU  - Baell, J
Y2  - 2021/01/06
Y1  - 2020/03/15
SN  - 0223-5234
UR  - http://hdl.handle.net/11343/258577
AB  - Parasitic roundworms (nematodes) are significant pathogens of humans and animals and cause substantive socioeconomic losses due to the diseases that they cause. The control of nematodes in livestock animals relies heavily on the use of anthelmintic drugs. However, their extensive use has led to a widespread problem of drug resistance in these worms. Thus, the discovery and development of novel chemical entities for the treatment of parasitic worms of humans and animals is needed. Herein, we describe our medicinal chemistry optimization efforts of a phenotypic hit against Haemonchus contortus based on a pyrrolidine-oxadiazole scaffold. This led to the identification of compounds with potent inhibitory activities (IC50 = 0.78-22.4 μM) on the motility and development of parasitic stages of H. contortus, and which were found to be highly selective in a mammalian cell counter-screen. These compounds could be used as suitable chemical tools for drug target identification or as lead compounds for further optimization.
LA  - English
PB  - ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
T1  - Synthesis and structure-activity relationship study of pyrrolidine-oxadiazoles as anthelmintics against Haemonchus contortus
DO  - 10.1016/j.ejmech.2020.112100
IS  - European Journal of Medicinal Chemistry
VL  - 190
OP  - 1102322
OP  - LP160100058
L1  - /bitstream/handle/11343/258577/2020%20Ruan%20et%20al%20Synthesis%20and%20structure-activity%20relationship%20study%20of%20pyrrolidine-oxadiazoles%20as.pdf?sequence=2&isAllowed=n
ER  -