Cheminformatic Profiling and Hit Prioritization of Natural Products with Activities against Methicillin-Resistant Staphylococcus aureus (MRSA)

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dc.contributor.authorOselusi, Samson, O
dc.contributor.authorEgieyeh, Samuel, A
dc.contributor.authorChristoffels, Alan
dc.date.accessioned2021-09-13T11:28:03Z
dc.date.available2021-09-13T11:28:03Z
dc.date.issued2021-06
dc.description.abstractSeveral natural products (NPs) have displayed varying in vitro activities against methicillin-resistant 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. Hit optimization strategies implemented on AMNPs with poor desirability scores led to the design of two compounds with improved desirability scores.en_US
dc.identifier.urihttps://doi.org/10.3390/molecules26123674
dc.identifier.urihttp://hdl.handle.net/10566/6658
dc.language.isoenen_US
dc.publisherMoleculesen_US
dc.subjectcheminformaticsen_US
dc.subjectprofilingen_US
dc.subjectnatural productsen_US
dc.subjectmethicillin-resistant Staphylococcus aureus (MRSA)en_US
dc.subjecthit prioritizationen_US
dc.subjecthit-to-lead optimizationen_US
dc.subjectdrug-likenessen_US
dc.subjectdesirability scoreen_US
dc.titleCheminformatic Profiling and Hit Prioritization of Natural Products with Activities against Methicillin-Resistant Staphylococcus aureus (MRSA)en_US
dc.typeArticleen_US

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