Azapyrimidine nucleosides: metabolism and inhibitory mechanisms.
Triazine nucleosides represent highly active compounds affecting different cellular processes. While 6-azauridine displays a rather selective inhibitory effect, biological action of 5-azacytidine reflects the polyvalent inhibitory mechanism of the drug (interaction with pyrimidine synthesis de novo, incorporation into RNA and DNA, depressed maturation of ribosomal RNA, inhibition of RNA and DNA methylation, etc.) and the analog displays pronounced cytostatic and immunosuppressive activity. 5-Aza-2'-deoxycytidine action is directed against DNA synthesis similar to that of 5-azacytosine arabinoside. N4-Substituted derivatives of 5-azacytidine affect gastric secretion and together with 5-azacytosine and 5-azacytidine represent a new type of drugs with antiulcer activity. 6-Amino-5-azacytosine nucleosides interfere with the metabolism of purines rather than pyrimidines as evidenced by the character of their inhibitory mechanism and measurement of conformation. 6-Azauridine (as 2',3',5'-triacetate) and 5-azacytidine were used with certain success in human chemotherapy, the first one as a drug affecting recalcitrant psoriasis, the second one for the treatment of different forms of leukemia. The inhibitory mechanisms of individual azapyrimidine nucleosides are discussed in relation to their known biological effects.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D001380:Azauridine / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D000077209:Decitabine; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D007942:Leukemia, Experimental / Q000378:metabolism; D051379:Mice; D012335:RNA, Ribosomal / Q000378:metabolism; D051381:Rats
D000970:Antineoplastic Agents; D012335:RNA, Ribosomal; C022121:fazarabine; D000077209:Decitabine; D001380:Azauridine; D004247:DNA; D001374:Azacitidine