Journal article

Synthesis and structure-activity relationship study of pyrrolidine-oxadiazoles as anthelmintics against Haemonchus contortus

Banfeng Ruan, Yuezhou Zhang, Solomon Tadesse, Sarah Preston, Aya C Taki, Abdul Jabbar, Andreas Hofmann, Yaqing Jiao, Jose Garcia-Bustos, Jitendra Harjani, Thuy Giang Le, Swapna Varghese, Silvia Teguh, Yiyue Xie, Jephthah Odiba, Min Hu, Robin B Gasser, Jonathan Baell

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER | Published : 2020

Abstract

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 i..

View full abstract

Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by Australian Research Council (ARC)


Funding Acknowledgements

For research at Monash University, the National Health and Medical Research Council of Australia (NHMRC) is thanked for Fellowship support for J.B. (2012-2016 Senior Research Fellowship #1020411, 2017-Principal Research Fellowship #1117602). The Australian Translational Medicinal Chemistry Facility (ATMCF) within Monash Institute of Pharmaceutical Sciences (MIPS) acknowledges the support of the Australian Government's National Collaborative Research Infrastructure Strategy (NCRIS) program via Therapeutic Innovation Australia (TIA). For research at the University of Melbourne, funding from the Australian Research Council (ARC; LP160100058), Yourgene Health, the National Health and Medical Research Council (NHMRC; APP1102322) of Australia is gratefully acknowledged; YJ held scholarships from the China Scholarship Council (CSC) and The University of Melbourne; SP was the recipient of a Pathfinder Fellowship (Wellcome),