1. In vitro anti-multidrug resistance activities of acyclic and cyclic disulfonamides in murine leukemia cells.
- Author
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Wakusawa S, Sawanishi H, and Hayashi H
- Subjects
- Animals, Antineoplastic Agents, Phytogenic administration & dosage, Antineoplastic Agents, Phytogenic pharmacokinetics, Antineoplastic Agents, Phytogenic pharmacology, Antineoplastic Combined Chemotherapy Protocols pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols pharmacology, Cycloheptanes administration & dosage, Cycloheptanes pharmacokinetics, Cycloheptanes pharmacology, Drug Resistance, Neoplasm, Ethylenes administration & dosage, Ethylenes pharmacokinetics, Ethylenes pharmacology, Leukemia P388 metabolism, Mice, Structure-Activity Relationship, Sulfonamides administration & dosage, Tumor Cells, Cultured, Vinblastine administration & dosage, Vinblastine pharmacokinetics, Vinblastine pharmacology, Drug Resistance, Multiple, Leukemia P388 drug therapy, Sulfonamides pharmacology
- Abstract
We synthesized seven acyclic ethylenedisulfonamides and twelve cyclic disulfonamides, 1, 5-bis(arenesulfonyl)-1, 3, 5-triazacycloheptanes, and compared their in vitro anti-multidrug resistance effects in P388/ADR multidrug-resistant cells which overexpress the multidrug transporter P-glycoprotein (P-gp). Acyclic disulfonamides with 4-methoxyphenyl, pyridyl, quinolyl, or isoquinolyl groups hardly influenced the sensitivity of P388/ADR cells to vinblastine (VLB), and cyclic disulfonamides with these aryl groups only slightly increased the sensitivity to VLB. Acyclic or cyclic disulfonamides with 4-chlorophenyl or naphthyl groups moderately potentiated the effect of VLB. The maximum effect was observed with 1, 5-bis(1-naphthale-nesulfonyl)-1, 3, 5-triazacycloheptan (B3). B3 enhanced the effects of vincristine, adriamycin, daunomycin and actinomycin D in P388/ADR cells, but not in sensitive P388 cells. B3 increased intracellular concentrations of VLB and adriamycin in P388/ADR cells. The expression of P-gp in P388/ADR cells was not affected by cultivation with B3 for 72 hours. These results indicated that the anti-multidrug resistance activities of B3 were dependent on its inhibitory effect on P-gp.
- Published
- 1998