Cheminformatic profiling and hit prioritization of natural products with activities against Methicillin-Resistant Staphylococcus Aureus (MRSA)
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Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
MPDI
Abstract
Several natural products (NPs) have displayed varying in vitro activities against methicillinresistant Staphylococcus aureus (MRSA). However, few of these compounds have not been developed
into potential antimicrobial drug candidates. This may be due to the high cost and tedious and
time-consuming process of conducting the necessary preclinical tests on these compounds. In this
study, cheminformatic profiling was performed on 111 anti-MRSA NPs (AMNPs), using a few orally
administered conventional drugs for MRSA (CDs) as reference, to identify compounds with prospects
to become drug candidates. This was followed by prioritizing these hits and identifying the liabilities
among the AMNPs for possible optimization. Cheminformatic profiling revealed that most of the
AMNPs were within the required drug-like region of the investigated properties. For example, more
than 76% of the AMNPs showed compliance with the Lipinski, Veber, and Egan predictive rules for
oral absorption and permeability. About 34% of the AMNPs showed the prospect to penetrate the
blood–brain barrier (BBB), an advantage over the CDs, which are generally non-permeant of BBB.
The analysis of toxicity revealed that 59% of the AMNPs might have negligible or no toxicity risks.
Structure–activity relationship (SAR) analysis revealed chemical groups that may be determinants of
the reported bioactivity of the compounds. A hit prioritization strategy using a novel “desirability
scoring function” was able to identify AMNPs with the desired drug-likeness.
Description
Keywords
Cheminformatics, Profiling, Natural products, Drug-likeness, Staphylococcus aureus
Citation
Oselusi, S. O. et al. (2021). Cheminformatic profiling and hit prioritization of natural products with activities against Methicillin-Resistant Staphylococcus Aureus (MRSA). Molecule, 26, 3674. https://doi.org/10.3390/ molecules26123674