IN-VITRO SUSCEPTIBILITY TESTING AND QUANT ITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS (QSAR) FOR THE DETERMINATION OF ANTIASPERGILLUS ACTIVITYFOR ANALOGS OF GLYCOLIPIDS

Objective. A quantitative structure activity relationship by neural ne twork was used to dispose the activity of new active molecules against Aspergillus fumigatus. A structure-activity relationship try to conne ct molecular properties represented by different parameters to antiasp ergillus activity. Lop P (lipophilicity parameter) and Rz/c (ratio bet ween number of heteroatoms and carbon atoms) are essential parameters, associated to connectivity or topological parameters, showing molecul ar length, ramification number, cycle number. Materials and methods. T he antifungal activity, represented by the concentration which reduce by 90 % the growth of A. fumigatus (IC90), is measured with an in vitr o test, based on glucose consumption. To make the relation between the structure and the antiaspergillus activity, we used 2 commercial comp ounds: amphotericin B and itraconazole with 13 amphiphilic glycolipid analogs. The polar head derive from glucose and lactose, the hydrocarb on chain also varying. We connected molecular parameters and antifunga l activity with a computer assisted system, based on artificial intell igence: a neural network. When the structure-activity relationship is done, with experimental results (IC90 measured with an in vitro test), we calculated predictive values for new antiaspergillus amphiphilic c ompounds, with molecular modeling, for the synthesis of interesting st ructures. Results. Absolute value of the difference between experiment al IC90 (measured with an in vitro test), and a predicted IC90 with a neural network, varies from 1.74 to 6.88 mu mol./l. Conclusion. The in terest in the use of neural network to predict antifungal activity of sugar derived amphiphilic compounds, against A. fumigatus was clearly shown in this study. With a neural network, it is possible to predict an IC90, before to synthesize a new molecule. The calculated IC90 are in agreement with the IC90 measured with an in vitro test.