Exploiting the Evolutionary Relationship between Malarial Parasites and Plants To Develop New Herbicides

Abstract

Herbicide resistance is driving aneed to develop new herbicides.T he evolutionary relationship between apicomplexan parasites,s uch as those causing malaria, and plants is close enough that many antimalarial drugs are herbicidal and so represent novel scaffolds for herbicide development. Using ac ompound library from the Medicines for Malaria Venture, the model plant Arabidopsis thaliana, and ap hysicochemical database of knownh erbicides,acompound was discovered that showed post-emergence herbicidal activity equal to commercial herbicides.U sing structure-activity analysis, important points for its potency were found. The compound was also tested and found to be active against common crop weeds.P hysiological profiling suggested the compound was ap hotosystem II inhibitor,r epresenting an ew scaffold for herbicide development. Overall this approach demonstrates the viability of using antimalarial compounds as lead compounds for the development of muchn eeded new herbicides.

Targeting plant DIHYDROFOLATE REDUCTASE with antifolates and mechanisms for genetic resistance

“…We recently demonstrated that antimalarial drugs, including the antifolates pyrimethamine and cycloguanil, have herbicidal activity against the model plant A. thaliana (Corral et al ., ,b, ). Given that both pyrimethamine and cycloguanil are known to target the DHFR domain of Plasmodium DHFR‐TS, it is probable that their herbicidal effect is via plant DHFR‐TS inhibition.…”

A herbicide structure–activity analysis of the antimalarial lead compound MMV007978 against Arabidopsis thaliana

“…14 the Malaria Box, that some of these lead compounds were also herbicidal, with one compound MMV006188 being active in soil and glasshouse studies, resulting in a new chemical scaffold for herbicidal development and a putative new mode of action. 15 We therefore explored a further portion of the Malaria Box and evaluated the materials as herbicidal-type compounds. If any hits were obtained that were useful these materials were put through a series of structural modifications, to gain insight into potency; the compound was also used in physiological assays to decipher a mode of action.…”

The power and potential of genomics in weed biology and management

“…Novel molecular targets may be discovered through computational approaches using the sequences of all expressed genes available from transcriptomes and genomes. Additionally, candidate molecules from other crop protection or medical sectors with known targets could be evaluated against plant targets using complete proteomes available from weed genomes, as has been conducted for antimalarial drugs as candidate herbicides using Arabidopsis as a model …”

“…Additionally, candidate molecules from other crop protection or medical sectors with known targets could be evaluated against plant targets using complete proteomes available from weed genomes, as has been conducted for antimalarial drugs as candidate herbicides using Arabidopsis as a model. 73,74 Potentially disruptive technologies such as RNAi and gene drive may provide new tools for weed management with facilitation by weed genomics. RNAi targets could function as herbicide synergists, and/or as stand-alone herbicides, depending on the efficiency of transcript silencing that can be achieved.…”