In Silico Studies on Selective MAO-B Inhibition and Microbiome Interaction of Novel Chalcone Derivatives for Autism Treatment

Finding: an effective treatment for autism spectrum disorder (ASD) requires a multifaceted approach. This includes the ability to remain in the digestive system to combat harmful microbes, pass through the bloodstream to neutralize free radicals, and cross the Blood-Brain Barrier (BBB). Crossing into the brain would inhibit certain enzymes, increase dopamine and serotonin levels, and reduce the byproducts of their interactions that contribute to neuroinflammation. In this work, we synthesized novel chalcone derivatives and examined their efficacy in inhibiting monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) to identify compounds that selectively inhibit MAO-B. After selecting four chalcone derivatives, these compounds underwent several tests, including testing their ability to interact with the active site within the enzyme (Molecular docking) and their affinity for it, and measuring their pharmacological properties in terms of solubility, absorption, plasma distribution, and penetration through both the gastrointestinal and blood-brain barriers. Given the gut-brain axis's importance in autism development, we conducted a hypothetical study to measure the compounds' interaction with two types of gut bacteria. The results showed that both selected compounds could promote the growth of beneficial bacteria and inhibit the growth of harmful bacteria in an in silico study. The safety of these compounds was later assessed by measuring their toxicity to living cells, paving the way for subsequent in vivo studies in laboratory animals. These tests were essential to ensure the compounds could withstand degradation and exert their intended effects at their target sites.