Molecular Topology for the Search of New Anti-MRSA Compounds

• Main Authors: Jose I. Bueso-Bordils, Pedro A. Alemán-López, Rafael Martín-Algarra, Maria J. Duart, Antonio Falcó, Gerardo M. Antón-Fos
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: International Journal of Molecular Sciences
• Subjects: antibacterial; antibiotics; anti-MRSA; computational chemistry; linear discriminant analysis; molecular topology
• Online Access: https://www.mdpi.com/1422-0067/22/11/5823
• ISSN: 1661-6596; 1422-0067

The variability of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), its rapid adaptive response against environmental changes, and its continued acquisition of antibiotic resistance determinants have made it commonplace in hospitals, where it causes the problem of multidrug resistance. In this study, we used molecular topology to develop several discriminant equations capable of classifying compounds according to their anti-MRSA activity. Topological indices were used as structural descriptors and their relationship with anti-MRSA activity was determined by applying linear discriminant analysis (LDA) on a group of quinolones and quinolone-like compounds. Four extra equations were constructed, named DF_MRSA1, DF_MRSA2, DF_MRSA3 and DF_MRSA4 (DF_MRSA was built in a previous study), all with good statistical parameters, such as Fisher–Snedecor F (>68 in all cases), Wilk’s lambda (<0.13 in all cases), and percentage of correct classification (>94% in all cases), which allows a reliable extrapolation prediction of antibacterial activity in any organic compound. The results obtained clearly reveal the high efficiency of combining molecular topology with LDA for the prediction of anti-MRSA activity.