1997 Fiscal Year Final Research Report Summary
Structure-activity relationship of triazacycloalkanes for reversal of antitumor multidrug resistance
| Project/Area Number |
08672570
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | Hokuriku University |
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Principal Investigator |
SAWANISHI Hiroyuki Hokuriku University, Pharmaceutical Science, Professor, 薬学部, 教授 (30100499)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Hirokazu Hokuriku University, Pharmaceutical Science, Assistant, 薬学部, 助手 (70257484)
WAKUSAWA Shinya Hokuriku University, Pharmaceutical Science, Associate Professor, 薬学部, 助教授 (30121297)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Cancer / Antitumor agent / Resistance / Sulfoneamide / Combination effect / In vitro / 1,3,5-triazacycloheptane |
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| Research Abstract |
We synthesized seven acyclic ethylenedisulfonamides and twelve 1,5-bis (arenesulfonyl)-1,3,5-triazacycloheptanes, and compared the effects on in vitro multidrug resistance and on intracellular accumulation of vinblastine (VLB) in P388/ADR multidrug-resistant cells which overexpress a multidrug transporter P-glycoprotein (P-gp). Any acyclic disulfonamides having 4-methoxyphenyl, pyridyl, quinolyl, or isoquinolyl groups hardly influenced the sensitivity to VLB in P388/ADR cells, and cyclic disulfonamides having such aryl groups only slightly increased the sensitivity to VLB.Acyclic or cyclic disulfonamides having 4-chlorophenyl or naphthyl groups moderately enhanced the effect of VLB.These compounds showed similar effects on intracellular accumulation of VLB.The maximum effect was observed in the case of 1,5-bis (1-naphthalenesulfonyl)-1,3,5-triazacycloheptane (B3). B3 enhanced the activity of vincristine, adriamycin, daunomycin, or actinomycin D in P388/ADR cells but not in sensitive P388 cells. The content of P-gp in P388/ADR cells was not affected by B3. B3 did not show any combined effects on the life-span of P388/ADR-bearing mice.
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