QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) OF A SERIES OF KETONE DERIVATIVES AS ANTI-CANDIDA ALBICANS

• Published in: International journal of drug discovery Vol. 3; no. 2; pp. 100 - 117
• Main Authors: MOTTA, LUIZ FREDERICO, ALMEIDA, WANDA PEREIRA
• Format: Journal Article
• Language: English
• Published: 30.12.2011
• Subjects: Candida albicans; Candidiasis; chemopreventive agents; Data processing; Immunosuppression; Ionization; ketones; Molecular modelling; Opportunist infection; Refractivity; Somatosensory evoked potentials; Structure-activity relationships; Thermodynamics
• ISSN: 0975-4423; 0975-914X
• DOI: 10.9735/0975-4423.3.2.100-117

Candidiasis is recognized worldwide as an opportunistic infection. The severities of the infection increase in immunosuppression conditions with possible occurrence of visceral mycoses and sometimes are widespread and systemic. Increased resistance in strains of Candida albicans is a major obstacle to antifungal therapy. The aim of this study was to correlate the chemical structure of compounds with experimental data from biological activity anti-Candida albicans. We performed classical QSAR for a series of twenty derivatives of ketone a-s unsaturated against resistant strains of Candida albicans. Ninety-four descriptors were calculated and multiparameter model was obtained through Partial Least Squares (PLS) method. The results showed that thermodynamic, dimensional and steric parameters are important in elucidating of action mechanism compounds. Four descriptors (molar refractivity, ionization potential, molecular length and Verloop B4) were selected and good model (n= 20; R2 = 0.776; SEC = 0.229; F(3,16) = 14.172; Q2LOO = 0.609; SEV = 0.295; Q2pred = 0.709; SEP = 0.091; k = 0.709; k' = 1.00; ?R20 - R'20? = 0.0009) was built with three latent variables describing 96.14% of the original information. Leave-N-out cross validation and Y-randomization analysis were performed in order to confirm the robustness of the model. The proposed model may provide a better understanding of the anti-Candida albicans activity of chalcones and can be used as guidance for proposition of new chemopreventive agents.