MOTIVATION: Metallothionein-III (MT-III) displays neuro-inhibitory activity and is involved in the repair of neuronal damage. An altered expression level of MT-III suggests that it could be a mitigating factor in Alzheimer's disease (AD) neuronal dysfunction. Currently there are limited marketed drugs available against MT-III. The inhibitors are mostly pseudo-peptide based with limited ADMET. In our present study, available database InterBioScreen (natural compounds) was screened out for MT-III. Pharmacodynamics and pharmacokinetic studies were performed. Molecular docking and simulations of top hit molecules were performed to study complex stability. RESULTS: Study reveals potent selective molecules that interact and form hydrogen bonds with amino acids Ser-6 and Lys-22 are common to established melatonin inhibitors for MT-III. These include DMHMIO, MCA B and s27533 derivatives. The ADMET profiling was better with comparable interaction energy values. It includes properties like blood brain barrier, hepatotoxicity, druggability, mutagenicity and carcinogenicity. Molecular dynamics studies were performed to validate our findings.

Biotechnology Division CSIR Central Institute of Medicinal and Aromatic Plants Lucknow 226015 India

Department of Biomedical Engineering Faculty of Electrical Engineering and Communication Brno University of Technology Technická 12 61200 Brno Czech Republic

Department of Pathological Physiology Faculty of Medicine Masaryk University Kamenice 5 Bld A18 625 00 Brno Czech Republic

International Clinical Research Center Center of Biomedical Engineering St Anne's University Hospital Brno and Department of Biomedical Engineering FEEC Brno University of Technology Brno Czech Republic

School of Biotechnology Yeungnam University Gyeongsan 712749 Republic of Korea

Citace poskytuje Crossref.org

The effect of Benzothiazolone-2 on the expression of Metallothionein-3 in modulating Alzheimer's disease