Fundamentals of Medicinal Chemistry

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and numerous channels connecting the intracellular fluid with the extracellular

fluid. These channels allow ions and other small molecules to travel from the

interior of the cell to its exterior and vice versa. Those whose primary function is

the transport of ions are known asion channels.

Most drugs act on the receptors and enzymes found in cell envelopes. How-

ever, a number of drugs act by either disrupting the structure of the cell

membranes and walls or inhibiting the formation of cell membranes and walls

or blocking ion channels. In general, drugs acting on microorganisms by either

disrupting the structures of membranes and walls or their synthesis appear to act

by

1. inhibiting the action of enzymes and other substances in the cell membrane

involved in the production of compounds necessary for maintaining the

integrity of the cell membrane,

2. inhibiting processes involved in the formation of the cell wall, resulting in an

incomplete cell wall, which leads to loss of vital cellular material and subse-

quent death of the cell,

3. forming channels through the cell wall or membrane, making it more porous,

which also results in the loss of vital cellular material and the death of the

cell, and

4. making the cell more porous by breaking down sections of the membrane.

All microorganisms have plasma membranes, which have characteristics in

common. Consequently, drugs can act by the same mechanism on quite differ-

ent classes of microorganism. For example, griseofulvin is both an antifungal

and an antibacterial agent (see section 7.2.1 and 7.2.2). Furthermore, the mem-

branes of prokaryotic cells exhibit a number of significantly different character-

istics to those of eukaroytic cells. It is these differences that must be exploited by

medicinal chemists if they are to find new drugs to treat microbiological infest-

ations.

7.2.1 Antifungal agents


Fungal infections usually involve the skin and mucous membranes of the body.

The fungal microorganisms are believed to damage the cell membrane, leading

to a loss of essential cellular components. Antifungal agents counter this attack

132 SELECTED EXAMPLES OF DRUG ACTION AT SOME COMMON TARGET AREAS

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