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Inhibitors of DNA and RNA formation from nucleotides; antimetabolites

The principal inhibitors of the insertion of nucleotides into DNA and RNA are structural analogs of purine and pyrimidines bases and of nucleosides, in this last case the structural modifications can be located on the base or the ribose.

Structural analogs are sufficiently close to endogenous molecules to be incorporate in the metabolism and sufficiently different to disturb it. So they can have several mechanisms of action: to lead to the formation of non functional DNA and RNA, to inhibit the DNA polymerase responsible of the DNA replication and thus of the cellular multiplication, to inhibit the transcription of DNA into RNA or that of RNA into DNA by the reverse transcriptase responsible of the replication of retroviruses.

They are given either in the form of base, or in the form of ribonucleoside. They disturb the synthesis of DNA or RNA after their conversion into triphosphate derivatives, thanks to enzymes of the host cell or of the virus present in the cell. Triphosphate derivatives themselves are not used, because being very polar, they penetrate poorly into cells.

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