Molecular Topology for the Discovery of New Broad-Spectrum Antibacterial Drugs

Abstract

In this study, molecular topology was used to develop several discriminant equations capable of classifying compounds according to their antibacterial activity. Topological indices were used as structural descriptors and their relation to antibacterial activity was determined by applying linear discriminant analysis (LDA) on a group of quinolones and quinolone-like compounds. Four equations were constructed, named DF1, DF2, DF3, and DF4, all with good statistical parameters such as Fisher–Snedecor’s F (over 25 in all cases), Wilk’s lambda (below 0.36 in all cases) and percentage of correct classification (over 80% in all cases), which allows a reliable extrapolation prediction of antibacterial activity in any organic compound. From the four discriminant functions, it can be extracted that the presence of sp3 carbons, ramifications, and secondary amine groups in a molecule enhance antibacterial activity, whereas the presence of 5-member rings, sp2 carbons, and sp2 oxygens hinder it. The results obtained clearly reveal the high efficiency of combining molecular topology with LDA for the prediction of antibacterial activity.

Water Activity Prediction in Sugar and Polyol Systems Using Theoretical Molecular Descriptors

“…Topological indices are two-dimensional descriptors derived from the topological representation of a molecule. In recent decades, molecular topology has emerged as a powerful approach to evaluate structure-activity relationships [23], especially in the fields of pharmacology and toxicology [24,25]. According to this approach, molecular structures are described in terms of the mathematical properties of their associated graphs.…”

Targeting bacterial growth in biofilm conditions: rational design of novel inhibitors to mitigate clinical and food contamination using QSAR

“…The reliability of this methodology in the antimicrobial field is established, with several noteworthy results reported in the literature. 24–27 Thanks to molecular topology, it is possible to develop QSAR predictive models that rely on a pure chemo-mathematical interpretation of the molecules and their relationship with a specific physicochemical or biological activity. 28 Graph theory is used to express chemical structures by means of numbers, making it possible to calculate ad hoc topological descriptors based on molecular connectivity features.…”

Molecular Topology for the Search of New Anti-MRSA Compounds

“…The effectiveness of the topological method has also been proven, having been successfully applied to different therapeutic groups, such as anti-HIV [ 29 ], antihistaminic [ 30 ], antitumor [ 31 ], anti-Alzheimer [ 32 ], and antibacterial agents [ 33 ].…”