Synthesis and Biological Activity of 6-Hydroxyguanidino-and 6-Hydroxyureidopurine And Their Ribonucleosides |
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| Authors: | Shib P. Dutta Ralph J. Bernacki Alexander Bloch Girish B. Chheda |
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| Affiliation: | 1. Departments of Biophysics Roswell Park Memorial Institute Buffalo , New York, 14263;2. Experimental Therapeuticst Roswell Park Memorial Institute Buffalo , New York, 14263 |
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| Abstract: | Abstract N 6 ?(1-hydroxyguanidino)purine IIa, and its 9-β-D-ribonucleoside derivative IIb were prepared by reacting at room temperature 6-hydroxyadenine Ia and 6-hydroxyadenosine Ib, with 1-guanyl-3,5-dimethylpyrazole nitrate in DMF. Refluxing IIa and IIb in 95% ethanol gave N6?(1-hydroxyureido)purine and its ribonucleoside derivative respectively; the latter compound was also obtained by refluxing Ib with 1-guanyl-3,5-dimethylpyrazole nitrate in ethanol. The two base analogs were inactive against L1210 cells in vitro, but the nucleoside derivatives inhibited the growth of these cells by 50% at 5 × 10 -6 and 6 × 10?7 M respectively. Compound IIb, at 200 mg/kg/day × 5, increased the life span of L1210-bearing DBA/2N mice by 57%. Cytofluorometric determinations showed that IIb inhibited cell growth in the G2 phase of the cell cycle. also found to inhibit adenosine deaminase activity with a Ki = 3.47 μM. |
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