Triaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate

Autor: Shridhar Narayanan, Laura M. Sanz, Sreenivasaiah Menasinakai, Kevin Hickling, Abhishek Srivastava, Sapna Morayya, Anandkumar Raichurkar, Vikas Patil, Stefan Kavanagh, María Belén Jiménez-Díaz, Ramanatha Saralaya, Vijender Panduga, Gajanan Shanbag, Eknath V. Bellale, Lyn Rosenbrier-Ribeiro, K.R. Prabhakar, Anisha Ambady, David Waterson, Nikhil Rautela, Kannan Murugan, Pavithra Viswanath, Peter Warner, Pamela Magistrado, Pravin Iyer, Dyann F. Wirth, Jayashree Puttur, Krishna Koushik, Sowmya Bharath, Nilanjana Roy Choudhury, Philipp P. Henrich, Olivia Coburn-Flynn, Suresh Solapure, Radha Nandishaiah, Balachandra Bandodkar, Kakoli Mukherjee, María Santos Martínez, Suresh Rudrapatna, David A. Fidock, Shahul Hameed P, Vinayak Hosagrahara, Monalisa Chatterji, Vasan K. Sambandamurthy, V. Balasubramanian, Sudhir Landge, Jitendar Reddy, Robert E. McLaughlin, Amanda K. Lukens, Adam Jeston Dudley, Disha Awasthy
Rok vydání: 2015
Předmět:
Zdroj: Nature Communications
ISSN: 2041-1723
Popis: The widespread emergence of Plasmodium falciparum (Pf) strains resistant to frontline agents has fuelled the search for fast-acting agents with novel mechanism of action. Here, we report the discovery and optimization of novel antimalarial compounds, the triaminopyrimidines (TAPs), which emerged from a phenotypic screen against the blood stages of Pf. The clinical candidate (compound 12) is efficacious in a mouse model of Pf malaria with an ED99
The emergence of resistant Plasmodium strains fuels the search for new antimalarials. Here, the authors present a new class of potent antimalarial compounds, the triaminopyrimidines, that display low toxicity and long half-life in animal models.
Databáze: OpenAIRE