A broad variety of structurally different hydrazone derivatives are designed and synthesized to alleviate the symptoms of preeclampsia via potential mitochondrial antioxidant therapy in Drs. Marianna and Bela Torok’s lab at UMass Boston. The compounds represent hydrazones with a variety of electron withdrawing and donating groups in the diaryl hydrazone skeleton, and larger derivatives with more extended delocalized electron structures (PMID: 39598676). The compounds are evaluated in a diverse selection of assays, including antioxidant assays to determine in vitro activity, as well as in cell biology assays to assess the effect of the compounds on human trophoblast cells with induced preeclampsia conditions. Our lab found the pretreatment with the prototypic compounds reduce mitochondrial-derived ROS production in H2O2-exposed trophoblasts cells confirming its mode of action and more importantly reduced sFLT-1 expression which is a key element in the development of preeclampsia (PMID: 40333076). These key data serve as a proof of concept for the applicability of the hydrazones in antioxidant therapy in preeclampsia models and ultimately developing them for human therapies in hypertensive disorders.
