Lapatinib, Nilotinib and Lomitapide Inhibit Haemozoin Formation in Malaria Parasites.

ABSTRACT: With the continued loss of antimalarials to resistance, drug repositioning may have a role in maximising efficiency and accelerating the discovery of new antimalarial drugs. Bayesian statistics was previously used as a tool to virtually screen USFDA approved drugs for predicted β-haematin (synthetic haemozoin) inhibition and in vitro antimalarial activity. Here, we report the experimental evaluation of nine of the highest ranked drugs, confirming the accuracy of the model by showing an overall 93% hit rate. Lapatinib, nilotinib, and lomitapide showed the best activity for inhibition of β-haematin formation and parasite growth and were found to inhibit haemozoin formation in the parasite, providing mechanistic insights into their mode of antimalarial action. We then screened the USFDA appro

SUBMITTER: de Sousa ACC 

PROVIDER: S-EPMC7180468 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature