Author

Nour Aldin Kahlous, Muhammad Al Mohdi Bawarish, Dr. Muhammad Arabi Sarhan, Dr. Manfred Kupper, Dr. Ali Hasaba, and Dr. Mazen Rajab

Published in

Assay and Drug Development Technologies Journal, Vol. 15 Issue 3 April 2017

Abstract

Discovering of new and effective antibiotics is a major issue facing scientists today. Luckily, the development of computer science offers new methods to overcome this issue. In this study, a set of computer software was used to predict the antibacterial activity of on antibiotic Food and Drug Administration (FDA)-approved drugs, and to explain their action by possible binding to well-known bacterial protein targets, along with testing their antibacterial activity against Gram-positive and Gram-negative bacteria. A three-dimensional virtual screening method that relies on chemical and shape similarity was applied using rapid overlay of chemical structures (ROCS) software to select candi-date compounds from the FDA-approved drugs database that share similarity with 17 known antibiotics. Then, to check their antibacterial activity, disk diffusion test was applied on Sta-phylococcus aureus and Escherichia coli. Finally, a protein docking method was applied using HYBRID software to predict the binding of the active candidate to the target receptor of its similar antibiotic. Of the 1,991 drugs that were screened, 34 had been selected and among them 10 drugs showed antibacterial activity, whereby drotaverine and metoclopramide activities were without precedent reports. Furthermore, the docking pro-cess predicted that diclofenac, drotaverine, (S)-flurbiprofen, (S)-ibuprofen, and indomethacin could bind to the protein target of their similar antibiotics. Nevertheless, their antibacterial activi-ties are weak compared with those of their similar antibiotics, which can be potentiated further by performing chemical mod-ifications on their structure.

Keywords: antibiotics, virtual screening, docking, antibacterial activity

Link to read full paper

http://online.liebertpub.com/doi/abs/10.1089/adt.2016.771