QSAR Study of Antimicrobial Activity of Some 3-Nitrocoumarins and Related Compounds

Abstract

A new class of antimicrobial agents, 3-nitrocoumarins and related compounds, has been chosen as a subject of the present study. In order to explore their activity and molecular properties that determine their antimicrobial effects, QSAR models have been proposed. Most of the 64 descriptors used for the development were extracted from semiempirical and density functional theory (DFT) founded calculations. For this study literature data containing results of microbiological activity screening of 33 coumarin derivatives against selected clinical isolates of C. albicans (CA) and S. aureus (SA) have been selected. Multivariate predictive models based on random forests (RF) and two hybrid classification approaches, genetic algorithms (GA) associated with either support vector machines (SVM) or k nearest neighbor (kNN), have been used for establishment of QSARs. An applied feature selection approach enabled two-dimensional linear separation of active and inactive compounds, which was a necessary tool for rational candidate design and descriptor relevance interpretation. Candidate molecules were checked by cross-validated models, and selected derivatives have been synthesized. Their antimicrobial activities were compared to antimicrobial activities of the representative derivatives from the original set in terms of minimal inhibitory concentration (MIC) against chosen SA and CA ATCC strains. High ranking of descriptors consistent with the degree of hydrolytic instability of selected compounds is common to models of antimicrobial activity against both microorganisms. However, descriptor ranking indicates different antimicrobial mechanisms of action of chosen coumarin derivatives against selected microbial species.

Complete assignment of the 1H and 13C NMR spectra of antimicrobial 4‐arylamino‐ 3‐nitrocoumarin derivatives

“…Several of these compounds, in particular 4‐arylamino‐3‐nitrocoumarin derivatives, showed promising activity in reducing the microbial growth in both fungal and bacterial cells 8, 9. Significant antimicrobial activity of a series of 4‐substituted‐3‐nitrocoumarins was also recently confirmed by a QSAR study 10. Previous research has shown that 4‐amino‐3‐nitrocoumarins, tested for pharmacological activity in mice and rabbits, had neurotropic activity, generally inhibiting spontaneous locomotor activity, decreasing hyperactivity induced by phenamine, and prolonging thiopental sleep 11.…”

Machine‐Learning Techniques Applied to Antibacterial Drug Discovery

“…In a second study from 2007, Debeljak et al sought to identify novel antibiotic coumarin derivatives (51). A random forest was generated using 64 quantum-mechanical and chemical descriptors calculated for 33 known coumarin-based antibiotics.…”

A small library of 4-(alkylamino)-3-nitrocoumarin derivatives with potent antimicrobial activity against gastrointestinal pathogens

“…Their function in the plant organism is far from clear, although some authors believe that they have growth regulatory functions, or that they act as fungistatic and bacteriostatic agents. 8 In connection with this, several arylamino-and (heteroarylamino)-3-nitrocoumarin derivatives were synthesized and their antimicrobial activity determined. [5][6][7] Significant antimicrobial activity of a series of 4-aryl-substituted 3-nitrocoumarins was recently demonstrated by Debeljak and co-workers.…”