The diterpene glucoside fusicoccin-A (FC-A) is a fungal phytotoxin that stabilizes the interaction of plant 14-3-3 protein and plasma membrane H+-ATPase by forming a stable ternary complex. Previous studies demonstrated that structurally modified FC-A derivatives exhibit significant antitumor activities but their synthesis involves an explosive reagent, limiting their utility and opportunities for further structure-activity-relationship studies. In this study, we synthesized a series of FC derivatives by introducing various substituents on the fusicoccan scaffold and on the glucoside moiety, and evaluated their stabilization effects on the binding of 14-3-3 to fluorescently labeled mode-1 and mode-3 phosphopeptides. The results showed that introducing an amino group at the 6\'-position of the glucoside moiety improves stabilization. Furthermore, cell-based evaluation demonstrated that 6\'-amino benzyl 21b exhibits higher antiproliferative activity than previously developed FC agents.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a progressive, fatal, neurodegenerative disease classified under transmissible spongiform encephalopathies (TSE) or prion diseases. It is characterized by long asymptomatic period followed by rapid clinical deterioration leading to the death within months. The disease is still under-reported in India.
OBJECTIVE: The aim of this study was to describe the clinical, radiological and electroencephalographic characteristics of eight cases of CJD encountered in MS Ramaiah Medical college and Hospital, Bangalore over the past 3 years (2010-2013). This was retrospective, observational, hospital-based study.
RESULTS: The mean age of patients was 66.6 years (range: 54-82) and there was female predominance (five patients). The main clinical manifestations were cognitive disturbance (8/8) and myoclonus (8/8), followed by behavioral disturbance (5/8), ataxia (5/8) and extra-pyramidal symptoms/signs (4/8). Time interval (mean) between onset of disease to death was 6.6 months (range: 3-14). Brain MRI abnormalities were noted in 6 patients: Fluid-attenuated inversion recovery hyperintensities with restriction on diffusion-weighted image/apparent diffusion coefficient (DWI/ADC) in caudate and putamen, and diffusion hyperintensities without restriction on ADC in parieto-occipital, frontal and temporal regions. Classical electroencephalogram (EEG) changes of periodic triphasic waves were seen in 87% of patients. The CSF 14-3-3 protein assay was positive in two patients (out of four). Seven cases were probable CJD and one was possible CJD.
CONCLUSIONS: A strong clinical suspicion aided by characteristic brain MRI and EEG abnormalities is essential for timely diagnosis of this fatal disease.