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QSAR analysis and molecular docking simulation of norepinephrine transporter (NET) inhibitors as anti-psychotic therapeutic agents.

ABSTRACT: The norepinephrine transporter (NET) is a Na+/Cl- coupled neurotransmitter transporter responsible for reuptake of released norepinephrine (NE) into nerve terminals in the brain, a key therapeutic used in the treatment of psychiatric disorders. A quantitative structural activity relationship (QSAR) study was performed on 50 compounds of NET inhibitors to investigate their inhibitory potencies against norepinephrine transporter as novel drugs for anti-psychotic disorders. The compounds were optimized by employing Density functional theory (DFT) with basis set of B3LYP/6-31G*. The genetic function Algorithm (GFA) approach was used to generate a highly predictive and statistically significant model with good correlation coefficient R2 Train = 0.952 Cross validated coefficient Q2 cv = 0.870 and adjusted squared correlation coefficient R2 adj = 0.898. The predictability and accuracy of the developed model was evaluated through external validation using test set compound, Y-randomization and applicability domain techniques. The results of Molecular docking analysis by using two neurotransmitter transporters PDB ID 2A65 (resolution = 1.65 Å) and PDB ID 4M48 (resolution = 2.955 Å) showed that two of the ligands (compound 12 and 44) having higher binding affinity were observed to inhibit the targets by forming hydrogen bonds and hydrophobic interactions with amino acids of the two receptors respectively. The results of these studies would provide important new insight into the molecular basis and structural requirements to design more potent and more specific therapeutic anti-psychotic drugs/agents.

SUBMITTER: Olasupo SB

PROVIDER: S-EPMC6806411 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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QSAR analysis and molecular docking simulation of norepinephrine transporter (NET) inhibitors as anti-psychotic therapeutic agents.

Olasupo Sabitu Babatunde SB Uzairu Adamu A Shallangwa Gideon G Uba Sani S

Heliyon 20191019 10

The norepinephrine transporter (NET) is a Na<sup>+</sup>/Cl<sup>-</sup> coupled neurotransmitter transporter responsible for reuptake of released norepinephrine (NE) into nerve terminals in the brain, a key therapeutic used in the treatment of psychiatric disorders. A quantitative structural activity relationship (QSAR) study was performed on 50 compounds of NET inhibitors to investigate their inhibitory potencies against norepinephrine transporter as novel drugs for anti-psychotic disorders. Th ...[more]

PMID: 31692668

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QSAR analysis and molecular docking simulation of norepinephrine transporter (NET) inhibitors as anti-psychotic therapeutic agents.

Publications

QSAR analysis and molecular docking simulation of norepinephrine transporter (NET) inhibitors as anti-psychotic therapeutic agents.

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