Koincidence antifungální a cytostatické aktivity u derivátů koruskanonu A a analog přírodních laktonů

• Main Author: Tichotová, Lucie
• Other Authors: Pour, Milan
• Format: Doctoral Thesis
• Language: Czech
• Published: 2011
• Online Access: http://www.nusl.cz/ntk/nusl-299388

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate: Mgr. Lucie Tichotová Supervisor: Prof. Milan Pour Title of Doctoral Thesis: Coincidence of antifungal and cytostatic activity of coruscanone A derivatives and analogues of natural lactones This Thesis was focused on the synthesis and biological evaluation of novel analogues of a natural antifungal compound, coruscanone A. For this purpose, a catalytic version of Knoevenagel condensation of cyclopent-4-ene-1,3-dione with aldehydes was developed. Evaluation of antifungal and cytostatic activity of the new derivatives revealed that antifungal activity of many compounds is accompanied by a cytostatic effect against certain tumour cell lines (CCRF-CEM). Subsequent examination of these arylidene analogues uncovered their decomposition in water medium under the conditions of in vitro testing. Therefore, stable analogues based on maleinimide were prepared by the Mitsunobu reaction. In these compounds, antifungal and antiproliferative effects occur simultaneously as well. N-2-indanylmaleinimide displayed the highest antifungal activity against A. fumigatus, while N-benzylmaleinimide had an excellent effect against HT-29 cells (IC50 = 0.6 μmol.l-1 ). Furthermore, cytostatic activity of...