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| The present invention relates to purified tetrahydropyrimidine derivatives and to pharmaceutical compositions comprising them. Two tetrahydropyrimidine derivatives, 2-methyl-4-carboxy-5-hydroxy-3,4,5,6 tetrahydropyrimidine (THP(A)) and 2-methyl-4-carboxy-3,4,5,6-tetrahydropyrimidine (THP(B)) accumulate intracellularly in Actinomycin D-producing bacteria, an antibiotic anti-tumor medication which disrupts normal RNA transcription. THP(A) and THP(B) appear to be a self-defense mechanism by which these bacteria protect themselves from the DNA damaging effects of Actinomycin D. The present invention provides pharmaceutical compositions comprising THP(A) and/or THP(B), and a pharmaceutically acceptable carrier. These compounds may protect DNA in non-tumor tissues from damaging by DNA-binding drugs, such as antitumor drugs.present relates purified tetrahydropyrimidine derivatives pharmaceutical compositions Actinomycins class antitumor antibiotics cancer chemotherapy prevent cell replication positioning themselves planar base pairs DNA preventing unwinding double helix inhibit transcription DNA-dependent RNA synthesis (Act D) known toxicity prevents general Lowering cytotoxic effective Two 2-methyl-4-carboxy-5-hydroxy-3 6-tetrahydropyrimidine (THP(A)) 2-methyl-4-carboxy-3 6-tetrahydropyrimidine(THP(B)) found accumulate intracellularly D-producing bacteria widely established self-defense mechanism respond resistance fully potent inhibitor parvulus produces normal course development synthesizing simultaneously seems transcriptional machinery characteristic cells |
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