Drugs acting on RNA

Several antibiotic agents are capable of acting on RNA molecules and interfering with transcription and translation. These are discussed in Chapter 10. 

In this chapter we have considered drugs which act on transcription, translation, and replication by acting directly on DNA and RNA. There are other drugs (e.g. nalidixic acid) which affect these processes, but since these drugs work by inhibiting enzymes rather than by a direct interaction with DNA or RNA, they have not been mentioned here. 

For several thousand years, man has used herbs and potions as medicines, but it is only since the mid-nineteenth century that serious efforts were made to isolate and purify the active principles of these remedies. Since then, a large variety of biologically active compounds have been obtained and their structures determined (e.g. morphine from opium, cocaine from coca leaves, quinine from the bark of the cinchona tree). 

These natural products became the lead compounds for a major synthetic effort where chemists made literally thousands of analogues in an attempt to improve on what Nature had provided. The vast majority of this work was carried out with no real design or reason, but out of the results came an appreciation of certain tactics which generally worked. A pattern for drug development evolved. This chapter attempts to show what that pattern is and the useful tactics which can be employed for developing drugs. 

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There are antibiotics which inhibit selectively the synthesis of one type of nucleic add. Their mechanism of action is entirely different from those discussed in the preceding sections. They do not bind to the DNA template, but directly impair the polymerizing enzyme. The pdnt is clearly established in the case of some new drugs acting on RNA polymerase. 

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