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Increasing evidence indicates that benzothiazoles and thioureas have the ability to inactivate reactive chemical species through their antioxidant activity. In this context, we designed and synthesized two benzothiazole-isothiourea derivatives, (E)-5-((benzo[d]thiazol-2-ylimino)(methylthio)methylamino)-2-hydroxybenzoic acid (compound 1) and (S,E)-2-((benzo[d]thiazol-2-ylimino)(methylthio)methylamino)-3-(4-hydroxyphenyl) propanoic acid (compound 2). The 2,2′-diphenyl-1-picrylhydrazyl radical reduction and Fenton reaction were used to evaluate the free radical scavenging activity of both compounds in vitro. The results indicated that compound 1 exhibited the highest scavenging activity. Hence, it was evaluated ex vivo using the initial phase of the acetaminophen-induced hepatotoxicity model. In particular, we demonstrated that compound 1 increased the reduced glutathione content and decreased the malondialdehyde levels. In addition, it was capable of inhibiting cytochrome P450 and producing a protective effect against the reactive intermediary N -acetyl- p -benzoquinoneimine. [ABSTRACT FROM AUTHOR]

Boron is a trace element with increasing importance in drug design. In this sense, boronic acids are emerging as therapeutic agents for several diseases. Herein, 3- and 4- acetamidophenylboronic acids and 4-acetamidophenylboronic acid pinacol ester were identified as potential inhibitors of acetylcholinesterase through docking assays on eel, rat, and human acetylcholinesterases indicating binding on the gorge region of the target enzymes. Then, these compounds were evaluated in vitro and in vivo. It was found these compounds showed ability to inhibit acetylcholinesterase as competitive and non-competitive inhibitors. But also, these compounds were non-toxic to PC12 cells at micromolar concentration, and they have the ability to protect those cells against damage by amyloid-beta. Noticeably, intraperitoneal administration of these boronic compounds to rats with the cognitive deficit induced by orchiectomy provided ameliorative effects on disrupted behavior and neuronal damage induced by hormonal deprivation. Additional approaches are required to evaluate the possibility of multiple mechanisms of action for the observed effects in the central nervous system. [Display omitted] • Boron is an attractive trace element modulating neuronal processes. • Boron-containing compounds modulate cognitive functioning. • Acetamidophenylboronic acids (APBAs) improved memory and decreasing neuronal damage in hippocampus. • APBAs are weak acetylcholinesterase inhibitors, but APBAs protected cells against damage by amyloid-beta. • APBAs were not toxic in PC12 cells at micromolar concentration. [ABSTRACT FROM AUTHOR]