Synthesis and fungitoxicity of some pyrimidine derivatives
A series of 12 pyrimidine derivatives were prepared and testedin vitro against growth, sporulation and nucleic acid content ofFusarium oxysporum f. sp.lycopersici andHelminthosporium oryzae. Introduction of a thiazole ring together with two aryl groups into 2-aminopyrimidine brought about drastic toxicity for both fungi. Pyrimidine derivatives with aryl groups alone were less toxic. Nitro groups were found to enhance the toxicity of the pyrimidine derivatives especially when substituted in the ortho-position of the aryl groups. Inhibition of nucleic acid synthesis of both fungi was attributed mainly to the presence of the thiazole ring.
6-Methylpurine-induced inhibition of sclerotia morphogenesis in Sclerotium rolfsii and its reversal by adenosine
In liquid synthetic medium inoculated with Sclerotium rolfsii (SR), addition of 6-methylpurine (MP, 50μg/ml) immediately after inoculation led to approximately 100% reduction in sclerotia production. Adenosine, and to a lesser extent guanosine, each at final concentration of 100μg/ml significantly reduced inhibition of sclerotia formation by SR in presence of 50μg/ml MP. Uridine and cytidine each at 100μg/ml had no such effect. The inhibition of sclerotia morphogenesis could be prevented by addition of 800μg/ml of adenosine together with 50μg/ml MP. Reversal by adenosine of MP-induced inhibition of sclerotia development was concentration dependent.
Antitumor activities of (2"R)-4'-O-tetrahydropyranyl-adriamycin (THP) and its combination with other antitumor agents on murine tumors.
(2''R)-4'-O-Tetrahydropyranyladriamycin (THP) is a new derivative of doxorubicin (adriamycin, ADM). The concentrations of THP and ADM required to inhibit by 50% the growth of a cultured L1210 cells was 0.003 microgram/ml and 0.016 microgram/ml, respectively. Various therapeutic designs of combinations of THP with other antitumor agents were investigated in vivo using the L1210 murine leukemia. The combination of THP with cytosine arabinoside (Ara-C), cyclocytidine hydrochloride (Cyclo-C), 6-mercaptopurine (6-MP) and cyclophosphamide (EX) showed a great effectiveness following daily intraperitoneal treatment from days 1 to 10. High therapeutic effects were also obtained with the combinations of THP with Ara-C, Cyclo-C, vincristine (VCR) and EX following intravenous combination therapy one day following implantation of L1210 leukemia. Schedule dependency and its therapeutic efficacy of THP were examined. THP showed almost the same antitumor activity on the solid-type sarcoma-180 or solid-type Ehrlich carcinoma as ADM by intraperitoneal or intravenous treatment. THP showed some superior activity to ADM in the advanced stage of L1210 leukemia. High antitumor activity of THP on murine leukemia L1210 has been reported by Tsuruo et al. (Cancer Res. 42: 1462-1467, 1982) and was also confirmed. THP gave many mice cures, especially in the intravenous treatment.