The 4-Aminomethylphenoxy-Benzoxaborole AN3057 as a Potential Treatment Option for Primary Amoebic Meningoencephalitis

Abstract

Primary amoebic meningoencephalitis is a rare but fatal central nervous system (CNS) disease caused by the “brain-eating amoeba” Naegleria fowleri . A major obstacle is the requirement for drugs with the ability to cross the blood-brain barrier, which are used in extremely high doses, cause severe side effects, and are usually ineffective.

Natural Terpenes Inhibit the Cytopathogenicity of Naegleria fowleri Causing Primary Amoebic Meningoencephalitis in the Human Cell Line Model

“…PAM has a reported 97% fatality rate, and from the 381 cases reported worldwide, only seven survivors were reported . A key factor in treating this infection is the rapid diagnosis .…”

“…1,11 PAM has a reported 97% fatality rate, 12 and from the 381 cases reported worldwide, only seven survivors were reported. 10 A key factor in treating this infection is the rapid diagnosis. 9 Currently used diagnosis techniques require testing the cerebrospinal fluid of the patient through immunohistochemical staining, polymerase chain reaction (PCR) testing, and microscopic examination to detectN.…”

“…The trophozoite is reported to penetrate the nasal cavity and travel to the cribriform through the olfactory nerve to reach the CNS.N. fowleri is known as a brain-eating amoeba as the parasite causes significant brain edema, damages neurons, and causes necrosis inside the CNS through several mechanisms such as releasing cytotoxic molecules and causing inflammatory reactions. , The clinical symptoms will appear 5–7 days after the initial exposure and are reported to be headaches, high fever, stiff neck, nausea, and vomiting, while during the final stages of the infection, patients also suffer from hallucinations, seizures, coma, and death. , …”

Cyanomethyl Vinyl Ethers Against Naegleria fowleri

“…9,24−28 Recently, the in vivo activity of some novel molecules such as 4-aminomethylphenoxy-benzoxaborole AN3057 or antifungals such as Posaconazole has been demonstrated in murine models. 29,30 On the other hand, studies have reported the biological activity of different cyano-substituted molecules in the last years, showing activity against several pathogenic organisms. For example, Quinoxalines have proven to be useful molecules for the development of new therapies against Tuberculosis and Chagas.…”

“…Regarding the treatment of PAM, the widely applied therapy involves a combination of amphotericin B and miltefosine and other drugs such as azoles in synergy, which have been shown to penetrate through the blood–brain barrier (BBB) and eliminate the amoebae at low concentrations. ,− Recently, the in vivo activity of some novel molecules such as 4-aminomethylphenoxy-benzoxaborole AN3057 or antifungals such as Posaconazole has been demonstrated in murine models. , …”