|Budget Amount *help
¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1998 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1997 : ¥2,100,000 (Direct Cost : ¥2,100,000)
So far, we found three compounds which exerted synergistic antiherpetic activities with acyclovir (ACV) and ganciclovir(GCV). Especially, of these agents, two diterpenoids, scopadulciol (SDC) and ponicidin (PND), potentiated the cell-killing activity of ACV and GCV in herpes simplex virus type 1(HSV-1) thymidine kinase (TK)-expressing cells. We report about these in detail as follows A naturally occuring flavone, 5,6,7-irimethoxyflavone (TMF), isolated from a plant Gallicarpa japonica, was subjected to antiviral assays . The agent exhibited inhibitory effects on HSV- 1 . TMF and ACV were synergic in their anti-HSV activities, During the evaluation of the effect of ponicidin(PND), which was isolated from a plant Rabdosia ternifolia . on the antiviral activities of ACV and GCV, the compound was found to preferentially activate HSV- 1 -specific TK but not cellular kinases. ln cultured human cancer cells transfected with HSV- 1 TK gene, cytotoxicities of ACV and GCV was strongly potentiated by PND.When the stability of the bioactivity of PND in the blood of mice was determined, the substance showed long-lasting effects on the potentiation of antiherpetic and cytotoxic activities of GCV.Another diterpenoid, SDC isolated from Scoparia dulcis, was also demonstrated as a potentiator of antiherpetic and cell-killing activities of ACV and GCV in in vilro experimental models. These data suggest that combined use of PND or SDC with ACV/GCV will be effective for cancer gene therapy because of more rapid and enhanced tumor elimination.