Therapeutic Potential of Thiophene-Based Chalcone Analog Against Acrylamide-Induced Neurotoxicity and Osteotoxicity.

Acrylamide (AR), a prevalent toxin in fried and baked foods, induces neurotoxicity and skeletal impairments through oxidative stress and apoptosis. A novel chalcone analog, 3-(5-bromo-2-hydroxyphenyl)-1-(5-chlorothiophen-2-yl)prop-2-en-1-one ( DC11 ), with its phenolic hydroxyl group, conjugated enone system, and chlorine atom in the thiophene ring, will contribute to the antioxidant properties. This study investigates the neuroprotective and osteoprotective effects of the chalcone derivative DC11 against AR-induced toxicity in zebrafish larvae. Our results show that DC11 effectively reduces oxidative stress, mitigates apoptosis, enhances bone mineralization, and improves locomotor functions in AR-exposed larvae. The phenolic hydroxyl group scavenges reactive oxygen species (ROS), while the enone system and chlorine atom enhance binding affinity and efficacy. Behavioral improvements in locomotion, coupled with biochemical and molecular evidence, underscore the comprehensive protective effects of DC11 against AR-induced toxicity. Although promising, further research is necessary to validate the efficacy and safety of DC11 in mammalian models and to elucidate its molecular mechanisms. Long-term studies are essential to understand potential side effects and therapeutic windows. This research identifies DC11 as a potent therapeutic candidate, addressing a critical gap in treating AR-induced neurotoxicity and osteotoxicity, and highlights its potential for mitigating these widespread health hazards.