Exploring the potential of pyrazoline containing molecules as Aβ aggregation inhibitors in Alzheimer’s disease
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Mihir Pramod Khambete
Abstract
Objectives
Alzheimer’s disease (AD) is a chronic and progressive neurodegenerative disease in which one of the most prominent pathological features is accumulation of amyloid (Aβ) plaques. This occurs due to the process of aggregation from monomeric to polymeric forms of Aβ peptide and thus represents one of the attractive targets to treat AD.
Methods
After initial evaluation of a set of molecules containing N-acetylpyrazoline moiety flanked by aromatic rings on both sides as Aβ aggregation inhibitors, the most potent molecules were further investigated for mechanistic insights. These were carried out by employing techniques such as circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM), in vitro PAMPA-BBB (Blood–Brain Barrier) assay and cytotoxicity evaluation.
Results
Two molecules among the exploratory set displayed Aβ aggregation inhibition comparable to standard curcumin. Among the follow-up molecules, several molecules displayed more inhibition than curcumin. These molecules displayed good inhibitory activity even at lower concentrations. CD and TEM confirmed the mechanism of Aβ aggregation. These molecules were found to alleviate Aβ induced cytotoxicity. BBB penetration studies highlighted the potential of these molecules to reach central nervous system (CNS).
Conclusions
Thus, several promising Aβ-aggregation inhibitors were obtained as a result of this study.
Funding source: DST-INSPIRE
Award Identifier / Grant number: IF130396
Acknowledgments
Author MK would like to thank DST-INSPIRE for funding the work reported in the manuscript via grant number IF130396.
Research funding: DST-INSPIRE (Via grant number IF130396).
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Ethical approval: The local Institutional Review Board deemed the study exempt from review.
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/dmpt-2019-0031).
© 2020 Walter de Gruyter GmbH, Berlin/Boston
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- Editorial
- Clinical implementation of pharmacogenetics and personalized drug prescription based on e-health: the MedeA initiative
- Review
- Pain pharmacogenetics
- Herbal preparations in the management of hypothyroidism in Unani medicine
- Mini Review
- Dapsone for Pneumocystis jirovecii pneumonia prophylaxis – applying theory to clinical practice with a focus on drug interactions
- Original Articles
- No effect of lipoic acid on catalytic activity of cytochrome P450 3A4
- Exploring the potential of pyrazoline containing molecules as Aβ aggregation inhibitors in Alzheimer’s disease
- Potential drug-drug interactions in ICU patients: a retrospective study
- Drug–drug interaction of rivaroxaban and calcium channel blockers in patients aged 80 years and older with nonvalvular atrial fibrillation
- Silver sulfadiazine loaded breathable hydrogel sponge for wound healing
- Protective effect of Cyperus esculentus (tiger nut) extract against scopolamine-induced memory loss and oxidative stress in mouse brain
- Role of purinergic signaling pathways in the adaptogenic-like activity of methyl jasmonate in rats exposed to unpredictable chronic mild stress
