IN-VITRO ANTI-MULTIDRUG RESISTANCE ACTIVITIES OF ACYCLIC AND CYCLIC DISULFONAMIDES IN MURINE LEUKEMIA-CELLS

We synthesized seven acyclic ethylenedisulfonamides and twelve cyclic disulfonamides, 1, 5-bis(arenesulfonyl)-1, 3, 5-triazacycloheptanes, a nd compared their in vitro anti-multidrug resistance effects in P388/A DR multidrug-resistant cells which overexpress the multidrug transport er P-glycoprotein (P-gp). Acyclic disulfonamides with 4-methoxyphenyl, pyridyl, quinolyl, or isoquinolyl groups hardly influenced the sensit ivity of P388/ADR cells to vinblastine (VLB), and cyclic disulfonamide s with these aryl groups only slightly increased the sensitivity to VL B. Acyclic or cyclic disulfonamides with 4-chlorophenyl or naphthyl gr oups moderately potentiated the effect of VLB. The maximum effect was observed with 1, 5-bis(1- naphthalenesulfonyl)-1, 3, 5-triazacyclohept an (B3). B3 enhanced the effects of vincristine, adriamycin, daunomyci n and actinomycin D in P388/ADR cells, but not in sensitive P388 cells . B3 increased intracellular concentrations of VLB and adriamycin in P 388/ADR cells. The expression of P-gp in P388/ADR cells was not affect ed by cultivation with B3 for 72 hours. These results indicated that t he anti-multidrug resistance activities of B3 were dependent on its in hibitory effect on P-gp.