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Title:
The search for compounds active against efflux pums of bacteria and tumor cells
Author:
Subject:
drug resistance ; efflux pumps inhibitors ; P glycoprotein (Pgp) ; hydantoin derivatives
Abstract:
This PhD dissertation was aimed at testing hydantoin derivatives synthesized in the Department of Technology and Biotechnology of Drugs of the Jagiellonian University Medical College in terms of their efficacy against bacteria and cancer cells. As far as bacteria are concerned, my research aimed to: - determine direct antibacterial activity of four groups of hydantoin derivatives against S. aureus and E. coli - determine ability of the compounds to restore efficacy of selected antibiotics For the active compounds, the research aimed to: - determine their mechanism of action by means of molecular modeling - check their toxicity in silico and in vitro using proliferation assay BM36 ((Z)-5-(naphthalen-2-ylmethylene)-2-(piperazin-1-yl)-3H-imidazol-4(5H)-one hydrochloride) turned out to be the most active compound against bacteria. Based on molecular modeling studies, it may be suggested that it prevents expression of a modified penicillin binding protein (PBP2a) whose presence makes S. aureus resistant to β lactam antibiotics. As far as cancer cells are concerned, my research aimed to test ability of four groups of hydantoin derivatives to inhibit an efflux pump, P-glycoprotein, in mouse lymphoma cells transfected with human P-pg gene using ethidium bromide accumulation assay. The most active compounds were arylidene hydantoins, especially phenylpiperazine deriva ; tives.
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Promoter:
Kieć-Kononowicz, Katarzyna ; Handzlik, Jadwiga