Journal article
Broad activity of diphenyleneiodonium analogues against Mycobacterium tuberculosis, malaria parasites and bacterial pathogens
N Nguyen, DW Wilson, G Nagalingam, JA Triccas, EK Schneider, J Li, T Velkov, J Baell
European Journal of Medicinal Chemistry | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER | Published : 2018
Abstract
In this study, a structure-activity relationship (SAR) compound series based on the NDH-2 inhibitor diphenyleneiodonium (DPI) was synthesised. Compounds were evaluated primarily for in vitro efficacy against Gram-positive and Gram-negative bacteria, commonly responsible for nosocomial and community acquired infections. In addition, we also assessed the activity of these compounds against Mycobacterium tuberculosis (Tuberculosis) and Plasmodium spp. (Malaria). This led to the discovery of highly potent compounds active against bacterial pathogens and malaria parasites in the low nanomolar range, several of which were significantly less toxic to mammalian cells.
Grants
Awarded by National Health and Medical Research Council
Funding Acknowledgements
T.V, J.B and J.L are supported by the Australian National Health and Medical Research Council (NHMRC). T.V. is an Australian NHMRC Industry Career Development. DW was supported by a NHMRC Peter Doherty Australian Biomedical Fellowship (APP1035715). Acknowledged is Australian Federal Government Education Investment Fund Super Science Initiative and the Victorian State Government, Victoria Science Agenda Investment Fund for infrastructure support, the facilities, and the scientific and technical assistance of the Australian Translational Medicinal Chemistry Facility (ATMCF), Monash Institute of Pharmaceutical Sciences (MIPS). ATMCF is supported by Therapeutic Innovation Australia (TIA). TIA is supported by the Australian Government through the National Collaborative Research Infrastructure Strategy (NCRIS) program.