Development of Diaryl Hydrazones for Alleviation of Mitochondrial Oxidative Stress in Preeclampsia
Year: 2025
Type: article
Abstract: Preeclampsia is a pregnancy-specific syndrome, linked to oxidative stress, affecting 5–8% of pregnancies, with no effective treatment available. Here, diaryl-hydrazones have been designed, synthesized, and investigated as mitochondria-targeting antioxidants to reduce placental oxidative stress and mitigate preeclampsia symptoms. The design, based on density functional theory studies, revealed that conjugated electron structure with the NH-motif appeared to explain their effect. Thirty compounds were synthesized and tested in three assays, where they exhibited excellent radical scavenging activity, significantly greater than that of the standard, Trolox. Based on the data, eight compounds were selected for cell-based assays. Oxidative stress was induced in human trophoblast cells and assessed whether the compounds reduced downstream antiangiogenic responses using ascorbic acid and MitoTEMPO as standards. The pretreatment with the hydrazones reduced mitochondrial superoxide and sFLT-1 production in H 2 O 2 -exposed trophoblast cells, indicating that mitochondrial oxidative stress and the anti-angiogenic response can be alleviated by these compounds.
Source: Journal of Medicinal Chemistry
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: American Heart Association, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute on Minority Health and Health Disparities, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1742481303, Mitochondria-targeting Novel Cationic Hydrazone Antioxidants for the Treatment of Preeclampsia, Organophosphate intoxication: effect of PARS inhibition, Radiocontrast Nephropathy: Redox Degradation Catalyst and Nitric Oxide Donor, G3863501579, G4066650261, Alleviation of Mitochondrial Oxidative Stress in Preeclampsia, G8117364093, Restoration of reduced nitric oxide bioavailability in Preeclampsia
OpenAlex ID: W4410155554