A new study published in the Journal of Medicinal Chemistry involved a phenotypic screening and identified a novel tetrazole-based series that shows fast action and has a relatively low propensity to develop high-level resistance.

Here, preliminary structure-activity relationships were established including identification of a subseries of related amides with antiplasmodial activity. Treatment of synchronized Plasmodium falciparum parasites was carried out with active analogues, that showed a pattern of intracellular inhibition of hemozoin (Hz) formation, similar to chloroquine (CQ). On the other hand, drug selections yielded only modest resistance, owing to the expression of the multidrug resistance gene 1 (pfmdr1). 

It was stated that the above finding can become the basis of future optimization efforts to develop a new malaria treatment.

Source: Journal of Medicinal Chemistry. 2021 Mar 11;64(5):2739-2761. doi: 10.1021/acs.jmedchem.0c02022.