Derivatization increases mosquito larvicidal activity of the sesquiterpene lactone parthenin isolated from the invasive weed Parthenium hysterophorus

BACKGROUND Extracts of the invasive weed Parthenium hysterophorus (Asteraceae) have been shown to possess larvicidal activity against a wide range of disease vectors. However, the phytochemicals responsible for the larvicidal activity from this plant remain unidentified. Here, we isolated the major sesquiterpene lactone, parthenin (1) from the plant and synthesized two derivatives [ethylene glycol (2) and azide (3) derivatives] targeting the α,β‐unsaturated carbonyl group, previously known to account for its biological activity such as toxicity towards cells and microorganism. All three compounds were screened for larvicidal activity against the African malaria vector Anopheles gambiae. RESULTS The larval mortality of ethylene glycol derivative (2) and 2α‐azidocoronopilin (3) were approximately two–four‐fold higher than that of parthenin (1) and neem oil with LC50 values of 37 and 66 mg L−1, respectively. Parthenin (1) and the positive control, neem oil, had comparable median lethal concentration (LC50) values of 154 and 121 mg L−1, respectively. In assays with binary combinations of the three compounds, larvicidal activity followed the order: parthenin (1) + 2α‐azidocoronopilin (3) (LC50 = 14 mg L−1) > parthenin (1) + ethylene glycol derivative (2) (LC50 = 109 mg L−1), > blend of 2α‐azidocoronopilin (3) and ethylene glycol derivative (2) (LC50 = 200 mg L−1). CONCLUSION Structural modification of parthenin (1) through addition of hydroxyl groups increases its larvicidal effects. These findings advance the use of structural modification approach in the development of lead chemical molecules for potential exploitation in larval source management. The study shows that mosquito larvicidal activity of parthenin, a sesquiterpene as is artemisinin, can be increased four‐fold by blending it with one of its derivatives. © 2020 Society of Chemical Industry