Nucleic acid drugs types

Stein D, Foster E, Huang SB, Weller D, Summerton J (1997) A spedfidty comparison of four antisense types morphoUno, 2 -0-methyl RNA, DNA, and phosphorothioate DNA, Antisense Nucleic Acid Drug Dev 7 151-157... 

Since the chemistry used in nucleic acid drug research has reached the current level, the major limiting step is delivery of the therapeutic, and several technological challenges need to be overcome in terms of stability, efficient and controlled delivery as well as addressing safety. So the limited number of currently registered products is by no means indicative of failure of these potentially revolutionary types of drugs. 

Stereochemistry is the chemistry of molecules in three dimensions. A clear understanding of stereochemistry is crucial for the study of complex molecules that are biologically important, e.g. proteins, carbohydrates and nucleic acids, and also drug molecules, especially in relation to their behaviour and pharmacological actions. Before we go into further detail, let us have a look at different types of isomerism that may exist in organic molecules. 

The sulfonamides include sulfadiazine, sulfamethizole, and similar agents (see Table 33-4). Sulfonamides interfere with bacterial nucleic acid production by disrupting folic acid synthesis in susceptible bacteria. Sulfonamide drugs are structurally similar to PABA, which is the substance used in the first step of folic acid synthesis in certain types of bacteria (see Fig. 33-2). Sulfonamides either directly inhibit the enzyme responsible for PABA utilization or become a substitute for PABA, which results in the abnormal synthesis of folic acid. In either case, folic acid synthesis is reduced, and bacterial nucleic acid synthesis is impaired. 

Pyrimidines are pyridines with two nitrogen atoms having a 1,3-relationship 66. They occur in nucleic acids as pyrimidine bases such as cytosine 67 and thymine 68 and you will notice that these are pyrimidones. An important new type of anti-cancer drug Glivec 69 has a pyrimidine core with a linked pyridine ring. 

Antimetabolites of nucleic acids as antitumor agents 91YGK989. Artemisinine (3,6,9-trimethyl-9,10h-epidioxyperhydropyrano[4,3,2-y/c] benzoxepin-2-one), a new type of antimalarial drug 92CSR85. 

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