Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity

International Journal of Molecular Sciences

Rodrigo S. A. de Araújo³  Felipe Q. S. Guerra³  Edeltrudes de O. Lima³  Carlos A. de Simone²  Josean F. Tavares³  Luciana Scotti¹  Marcus T. Scotti⁴  Thiago M. de Aquino⁵  Ricardo O. de Moura¹  Francisco J. B. Mendon๺¹ 

[1] Laboratory of Synthesis and Drug Delivery, Biological Science Department, State University of Paraíba, João Pessoa 58020-540, PB, Brazil; E-Mails:;Department of Physics and Informatics, Physical Institute of São Carlos, University of São Paulo, São Carlos 13560-970, SP, Brazil; E-Mail:;Pharmaceutical Science Department, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil; E-Mails:;Engineering and Environment Department, Federal University of Paraíba, Campus IV, Rio Tinto 58297-000, PB, Brazil; E-Mail:;Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceió 57072-970, AL, Brazil; E-Mail:

关键词: coumarin derivatives;    antifungal activity;    Aspergillus sp.;    structure-activity relationships (SAR);    molecular modeling;    principal component analysis (PCA);    partial least squares regression (PLS);    density functional theory (DFT);   

DOI  :  10.3390/ijms14011293

来源: mdpi

【 摘 要 】

The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 μg/mL. The structure-activity relationships (SAR) study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO₂ and/or acetate) favor activity. These findings were confirmed using density functional theory (DFT), when calculating the LUMO density. In Principal Component Analysis (PCA), two significant principal components (PCs) explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS) model showed an r² of 0.86 and q²_cv of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity.

【 授权许可】

CC BY   
© 2013 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.