Preprint Article Version 1 This version not peer reviewed

In Silico Screening and Analysis of Potential Inhibitors of Arylamine N-Acetyltransferases (NATs) from the Traditional Chinese Medicine: A Study Using Free Available Tools

Version 1 : Received: 29 June 2017 / Approved: 30 June 2017 / Online: 30 June 2017 (11:36:22 CEST)

How to cite: Azevedo, F.; Richardt, J.; Oliveira, M.; Araujo, I.; Oliveira, R.; Baptista, L.; Amorim, H. In Silico Screening and Analysis of Potential Inhibitors of Arylamine N-Acetyltransferases (NATs) from the Traditional Chinese Medicine: A Study Using Free Available Tools. Preprints 2017, 2017060132 (doi: 10.20944/preprints201706.0132.v1). Azevedo, F.; Richardt, J.; Oliveira, M.; Araujo, I.; Oliveira, R.; Baptista, L.; Amorim, H. In Silico Screening and Analysis of Potential Inhibitors of Arylamine N-Acetyltransferases (NATs) from the Traditional Chinese Medicine: A Study Using Free Available Tools. Preprints 2017, 2017060132 (doi: 10.20944/preprints201706.0132.v1).

Abstract

Arylamine N-acetyltransferases (NATs) are cytosolic enzymes, highly polymorphic, present in both eukaryotes and prokaryotes. These enzymes play an important role in the detoxification and activation of xenobiotics as well as in the synthesis of endogenous compounds. Specific NATs have been pointed out in the literature as possible therapeutic targets. In particular, the human NAT1, for the treatment of certain cancers, and the NAT from M. tuberculosis (TBNAT), for the treatment of tuberculosis. This paper describes an in silico approach to prospect and select potentially inhibitors of NAT1 and TBNAT from the Traditional Chinese Medicine (TCM) using free available tools. A library with ligands from TCM was previously screened in order to select only compounds with optimal pharmacological properties. The affinity of the selected ligands with respect to NAT enzymes was then evaluated by virtual screening (VS). Subsequently, the complexes with the best ligands were submitted to molecular dynamics (MD) simulations aiming to obtain better quality information on affinity and selectivity. The results for one specific ligand, ZINC14690579, indicated its potential for affinity and selectivity. ZINC14690579 structure may represent the discovery of a new scaffold for future development of NAT inhibitors.

Subject Areas

arylamine N-acetyltransferases; cancer; tuberculosis; drug discovery; traditional Chinese medicine; virtual screening; molecular dynamics simulation; MM-PBSA

Readers' Comments and Ratings (0)

Leave a public comment
Send a private comment to the author(s)
Rate this article
Views 0
Downloads 0
Comments 0
Metrics 0
Leave a public comment

×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.