ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

QSAR, docking studies and toxicology prediction of isoquinoline derivatives as leucine aminopeptidase inhibitors

Joanna Ziemska, Jolanta Solecka, and Małgorzata Jarończyk

National Institute of Public Health, National Institute of Hygiene, Warsaw, Poland

E-mail: jziemska@pzh.gov.pl

Abstract: Here, we report a theoretical study on leucine aminopeptidase (LAP) inhibitors. 3D quantitative structure–activity relationship (3D-QSAR) studies were carried out on a series of known substituted dihydroisoquinoline derivatives and other chemical compounds with inhibitory activity towards LAP. We also designed a series of 33 isoquinoline derivatives containing phosphonic/phosphinic acid moieties and applied the 3D-QSAR model to evaluate their possible LAP inhibitory activity. In silico studies showed that these compounds interact with zinc ions, form H-bonds and exhibit hydrophobic interactions with amino acids in the LAP binding pocket as well as present high scoring values. The obtained QSAR data provide useful information about the structural characteristics of inhibitors which contribute to their inhibitory potency.

Keywords: Leucine aminopeptidase; LAP inhibitors; Isoquinoline derivatives; Field-based QSAR

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-017-0251-3

Chemical Papers 71 (12) 2557–2568 (2017)