Production of Highly Active Antiparasitic Compounds from the Controlled Halogenation of the <i>Arrabidaea brachypoda</i> Crude Plant Extract

Abstract

Direct halogenation of phenolic compounds present in the CH₂Cl₂ extract of the roots of <i>Arrabidaea brachypoda</i> was investigated to enhance chemodiversity. The approach is based on eco-friendly reactions using NaBr, NaI, and NaCl in aqueous media to generate multiple "unnatural" halogenated natural products from crude extracts. The halogenation reactions, monitored by UHPLC-PDA-ELSD-MS, were optimized to generate mono-, di-, or trihalogenated derivatives. To isolate these compounds, the reactions were scaled up and the halogenated analogues were isolated by semipreparative HPLC-UV and fully characterized by NMR and HR-MS data. All of the original 16 halogenated derivatives were evaluated for their antiparasitic activities against the parasites <i>Leishmania amazonensis</i> and <i>Trypanosoma cruzi</i>. Compounds presenting selective antiparasitic activities against one or both parasites with IC₅₀ values comparable to the reference were identified.