RESUMEN
Malaria remains one of the deadliest infectious diseases worldwide and continues to infect hundreds of millions of individuals each year. Here we report the discovery and derivatization of a series of 2,6-dibenzylidenecyclohexanones targeting the chloroquine-sensitive 3D7 strain of Plasmodium falciparum . While the initial lead compound displayed significant toxicity in a human cell proliferation assay, we were able to identify a derivative with no detectable toxicity and sub-micromolar potency.
Asunto(s)
Antimaláricos/farmacología , Cloroquina/farmacología , Plasmodium falciparum/efectos de los fármacos , Antimaláricos/síntesis química , Antimaláricos/química , Proliferación Celular/efectos de los fármacos , Cloroquina/síntesis química , Cloroquina/química , Relación Dosis-Respuesta a Droga , Fibroblastos/efectos de los fármacos , Humanos , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Relación Estructura-ActividadRESUMEN
Objective: Vestibular migraine (VM) is a diagnostic challenge. Visually enhanced vestibulo-ocular reflex (VVOR) gain, a measure of the visual-vestibular interaction, has been proposed as a tool for diagnosing VM. This study seeks to evaluate VVOR gain's diagnostic capability to predict VM and to compare the phenotypes of vestibular patients with elevated versus normal/low VVOR gain. Methods: A retrospective review of consecutive adult patients at a dizziness clinic from October 2016 and December 2020 was conducted. VVOR gain's diagnostic performance was assessed with the area under the receiver operating characteristic (AUROC) analysis. Demographic factors and clinical presentations were compared between vestibular patients with elevated versus normal/low VVOR gain. Results: One hundred forty patients (70 with VM) were analyzed. VVOR gain was elevated in 68.6% of patients with VM, compared to 52.9% of patients without VM (p = .057). The AUROC of VVOR gain was 0.5902 (95% confidence interval: 0.4958-0.6846). Vestibular patients with elevated VVOR gain were younger than those with normal/low VVOR gain (mean age 50 vs. 62, p < .0001). A higher proportion of subjects with elevated VVOR gain had symptoms triggered by certain foods (17.6% vs. 5.5%, p = .040) and experienced sound sensitivity (34.1% vs. 18.2%, p = .040) and motion sensitivity (23.5% vs. 9.1%, p = .041). A greater proportion of VM patients with elevated VVOR gain were triggered by certain foods (27.1% vs. 0%, p = .006). Conclusion: VVOR gain alone has limited ability to discriminate VM from other vestibular conditions and must be interpreted carefully. VVOR gain elevation may be associated with food triggers and motion and sound sensitivity. Level of Evidence: IV.