Ivermectin metabolites reduce Anopheles survival
Ivermectin is a natural product derived broad spectrum antiparasitic drug, primarily deployed to combat parasitic worms in veterinary and human medicine. Due to its ability to kill the parasite Plasmodium falciparum that causes malaria, it has emerged as a potentially useful malaria transmission tool [1,2].
A paper by Kevin Kobylinski and colleagues looks at the activity of key metabolites of ivermectin to explain why the mosquito-lethal effect of ivermectin in clinical trials exceeds that predicted from in vitro laboratory experiments .
In the study, the three primary human ivermectin metabolites (M1, M3, and M6) investigated were shown to each have a mosquito-lethal effect similar to that of the ivermectin parent compound for two primary malaria vectors. This was the first time that the mosquito-lethal effect of ivermectin metabolites on Anopheles survival has been investigated in an in vitro system.
As part of this project Hypha made the two O-demethylated metabolites M1 and M6 using microbial biotransformation. These metabolites had previously not been possible to make by chemical synthesis. Structures were confirmed by NMR spectroscopy.
 Crump, A. Ivermectin: enigmatic multifaceted ‘wonder’ drug continues to surprise and exceed expectations. J Antibiot 70, 495–505 (2017). https://doi.org/10.1038/ja.2017.11
 Chaccour, C. and Rabinovich, N.R. Advancing the repurposing of ivermectin for malaria. The Lancet 393 (10180), 1480-1481 (2019). https://doi.org/10.1016/S0140-6736(18)32613-8
 Kobylinski, K.C., Tipthara, P., Wamaket, N. et al. Ivermectin metabolites reduce Anopheles survival. Sci Rep 13, 8131 (2023). https://doi.org/10.1038/s41598-023-34719-2