EFFECT OF NEW THIOACRIDINE DERIVATIVES ON P-GP FUNCTION AND ON MDR1 GENE-EXPRESSION

We studied the effect of thioacridine derivatives on the function of P -glycoprotein in MDR mouse T-lymphoma cell line L5178 and in MDR human leukemia cell line K562/ADR by rhodamine 123 uptake assay. The effect of some selected thioacridines was also investigated on the expressio n of the mdr1 gene. Expression was analysed by RT-PCR Two compounds: 3 -amino-9-thio-(4'-nitrobenzyl)acridinone and 2,7-dimethoxy-9-thio-(2'- diethylaminoethyl) acridinone were able to block the function of the P -gp, and also to decrease significantly md I gene expression. Because these two derivatives exert their positive effects as reversing agents they could be potential candidate anticancer agents for further inves tigation. The thioacridines, which do not affect P-gp function do not affect or increase the expression of mdr1 gene. Our results showed the structure-activity relationships of these compounds, providing a dire ction for the development of new, more active compounds.