Virtual screening, ADMET profiling, molecular docking and
dynamics approaches to search for potent selective natural
molecules based inhibitors against metallothionein-III to study
Alzheimer's disease

J 2015

Virtual screening, ADMET profiling, molecular docking and dynamics approaches to search for potent selective natural molecules based inhibitors against metallothionein-III to study Alzheimer's disease

ROY, Sudeep; Akhil KUMAR; Mohd Hassan BAIG; Michal MASAŘÍK; Ivo PROVAZNÍK et al.

Základní údaje

Originální název

Virtual screening, ADMET profiling, molecular docking and dynamics approaches to search for potent selective natural molecules based inhibitors against metallothionein-III to study Alzheimer's disease

Autoři

ROY, Sudeep; Akhil KUMAR; Mohd Hassan BAIG; Michal MASAŘÍK a Ivo PROVAZNÍK

Vydání

Methods, San Diego, Academic Press Inc. Elsevier Science, 2015, 1046-2023

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.503

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/15:00083935

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

Alzheimer's disease; Metallothionein-III; Virtual screening; ADMET; Molecular dynamics

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 22. 9. 2015 15:28, Soňa Böhmová

Anotace

V originále

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.

Citovat

ROY, Sudeep; Akhil KUMAR; Mohd Hassan BAIG; Michal MASAŘÍK a Ivo PROVAZNÍK. Virtual screening, ADMET profiling, molecular docking and dynamics approaches to search for potent selective natural molecules based inhibitors against metallothionein-III to study Alzheimer's disease. Methods. San Diego: Academic Press Inc. Elsevier Science, 2015, roč. 83, "15 July 2015", s. 105-110. ISSN 1046-2023. Dostupné z: https://doi.org/10.1016/j.ymeth.2015.04.021.

@article{1311834,
   author = {Roy, Sudeep and Kumar, Akhil and Baig, Mohd Hassan and Masařík, Michal and Provazník, Ivo},
   article_location = {San Diego},
   article_number = {"15 July 2015"},
   doi = {https://doi.org/10.1016/j.ymeth.2015.04.021},
   keywords = {Alzheimer's disease; Metallothionein-III; Virtual screening; ADMET; Molecular dynamics},
   language = {eng},
   issn = {1046-2023},
   journal = {Methods},
   title = {Virtual screening, ADMET profiling, molecular docking and dynamics approaches to search for potent selective natural molecules based inhibitors against metallothionein-III to study Alzheimer's disease},
   volume = {83},
   year = {2015}
}

TY  - JOUR
ID  - 1311834
AU  - Roy, Sudeep - Kumar, Akhil - Baig, Mohd Hassan - Masařík, Michal - Provazník, Ivo
PY  - 2015
TI  - Virtual screening, ADMET profiling, molecular docking and dynamics approaches to search for potent selective natural molecules based inhibitors against metallothionein-III to study Alzheimer's disease
JF  - Methods
VL  - 83
IS  - "15 July 2015"
SP  - 105-110
EP  - 105-110
PB  - Academic Press Inc. Elsevier Science
SN  - 10462023
KW  - Alzheimer's disease
KW  - Metallothionein-III
KW  - Virtual screening
KW  - ADMET
KW  - Molecular dynamics
N2  - 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.
ER  -

ROY, Sudeep; Akhil KUMAR; Mohd Hassan BAIG; Michal MASAŘÍK a Ivo PROVAZNÍK. Virtual screening, ADMET profiling, molecular docking and dynamics approaches to search for potent selective natural molecules based inhibitors against metallothionein-III to study Alzheimer's disease. \textit{Methods}. San Diego: Academic Press Inc. Elsevier Science, 2015, roč.~83, ''15 July 2015'', s.~105-110. ISSN~1046-2023. Dostupné z: https://doi.org/10.1016/j.ymeth.2015.04.021.

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