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Open AccessArticle

In Silico Screening for Novel Leucine Aminopeptidase Inhibitors with 3,4-Dihydroisoquinoline Scaffold

1
National Institute of Public Health–National Institute of Hygiene, Chocimska 24, 00-791 Warsaw, Poland
2
National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Sandra Gemma
Molecules 2020, 25(7), 1753; https://doi.org/10.3390/molecules25071753
Received: 18 March 2020 / Revised: 6 April 2020 / Accepted: 8 April 2020 / Published: 10 April 2020
(This article belongs to the Special Issue Structure-Based Design of Biologically Active Compounds)
Cancers are the leading cause of deaths worldwide. In 2018, an estimated 18.1 million new cancer cases and 9.6 million cancer-related deaths occurred globally. Several previous studies have shown that the enzyme, leucine aminopeptidase is involved in pathological conditions such as cancer. On the basis of the knowledge that isoquinoline alkaloids have antiproliferative activity and inhibitory activity towards leucine aminopeptidase, the present study was conducted a study which involved database search, virtual screening, and design of new potential leucine aminopeptidase inhibitors with a scaffold based on 3,4-dihydroisoquinoline. These compounds were then filtered through Lipinski’s “rule of five,” and 25 081 of them were then subjected to molecular docking. Next, three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed for the selected group of compounds with the best binding score results. The developed model, calculated by leave-one-out method, showed acceptable predictive and descriptive capability as represented by standard statistical parameters r2 (0.997) and q2 (0.717). Further, 35 compounds were identified to have an excellent predictive reliability. Finally, nine selected compounds were evaluated for drug-likeness and different pharmacokinetics parameters such as absorption, distribution, metabolism, excretion, and toxicity. Our methodology suggested that compounds with 3,4-dihydroisoquinoline moiety were potentially active in inhibiting leucine aminopeptidase and could be used for further in-depth in vitro and in vivo studies. View Full-Text
Keywords: leucine aminopeptidase inhibitor; 3,4-dihydroisoquinoline; molecular docking; structure-based drug design; 3D-QSAR; drug-likeness leucine aminopeptidase inhibitor; 3,4-dihydroisoquinoline; molecular docking; structure-based drug design; 3D-QSAR; drug-likeness
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MDPI and ACS Style

Ziemska, J.; Solecka, J.; Jarończyk, M. In Silico Screening for Novel Leucine Aminopeptidase Inhibitors with 3,4-Dihydroisoquinoline Scaffold. Molecules 2020, 25, 1753. https://doi.org/10.3390/molecules25071753

AMA Style

Ziemska J, Solecka J, Jarończyk M. In Silico Screening for Novel Leucine Aminopeptidase Inhibitors with 3,4-Dihydroisoquinoline Scaffold. Molecules. 2020; 25(7):1753. https://doi.org/10.3390/molecules25071753

Chicago/Turabian Style

Ziemska, Joanna; Solecka, Jolanta; Jarończyk, Małgorzata. 2020. "In Silico Screening for Novel Leucine Aminopeptidase Inhibitors with 3,4-Dihydroisoquinoline Scaffold" Molecules 25, no. 7: 1753. https://doi.org/10.3390/molecules25071753

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