SULFONAMIDES: MECHANISM OF ACTION, CLASSIFICATION AND EXAMPLES - CHEMISTRY - 2025

The sulfonamides are species whose structure is formed by the sulfonyl moiety (RS (= O) ₂ -R '), wherein both oxygen atoms are linked by double bonds to the sulfur atom, and the amino functional group (R NR'R ''), where R, R 'and R' 'are substituent atoms or groups single bonded to the nitrogen atom.

Likewise, this functional group forms compounds that have the same name (whose general formula is represented as RS (= O) ₂ -NH ₂), which constitute substances that are precursors of some groups of drugs.

In the mid-1935s, the German-born scientist Gerhard Domagk, specializing in the areas of pathology and bacteriology, found the first species belonging to the sulfonamides.

This compound was called Prontosil rubrum and, together with his research, it earned him the merit of the Nobel Prize in Physiology or Medicine almost five years after its discovery.

Mechanism of action

In the case of drugs produced from these chemical substances, they have bacteriostatic properties (which paralyze the growth of bacteria) of wide applicability, especially for the elimination of most of the organisms considered as Gram positive and Gram negative.

In this way, the structure of sulfonamides is quite similar to that of para-aminobenzoic acid (better known as PABA, for its acronym in English), which is considered essential for the process of biosynthesis of folic acid in bacterial organisms, for which sulfonamides appear to be selectively toxic.

For this reason, there is a competition between both compounds for the inhibition of the enzymatic species called dihydrofolate synthase, and they produce the blockade of dihydrofolic acid synthesis (DHFA), which is essential to synthesize nucleic acids.

When the biosynthetic process of the coenzymatic folate species is blocked in bacterial organisms, the inhibition of their growth and reproduction is generated.

Despite this, the clinical application of sulfonamides has fallen into disuse for many treatments, so it is combined with trimethoprim (belonging to the diaminopyrimidines) for the production of a large number of drugs.

Classification

Sulfonamides have different properties and characteristics depending on their structural configuration, which depends on the atoms that make up the R chains of the molecule and their arrangement. They can be classified into three main classes:

Sultams

They belong to the group of sulfonamides with a cyclic structure, which are produced in a similar way to other types of sulfonamides, commonly through the oxidation process of thiols or disulfides that have formed bonds with amines, in a single container.

Another way to obtain these compounds that manifest bioactivity involves the preliminary formation of a linear chain sulfonamide, where later bonds between carbon atoms are originated to form cyclic species.

These species include sulfanilamide (a precursor to sulfa drugs), sultiame (with anticonvulsant effects), and ampiroxicam (with anti-inflammatory properties).

Sulfinamides

These substances have a structure represented as R (S = O) NHR), in which the sulfur atom is linked to an oxygen through a double bond, and through single bonds to the carbon atom of the R group and to the nitrogen of the group NHR.

In addition, these belong to the group of amides that come from other compounds called sulfinic acids, whose general formula is represented as R (S = O) OH, where the sulfur atom is linked by a double bond to an oxygen atom and by bonds simple with the R substituent and the OH group.

Some sulfinamides that have chiral properties -such as para-toluenesulfinamide- are considered of great importance for asymmetric synthesis processes.

Disulfonimides

The structure of disulfonimides has been established as RS (= O) ₂ -N (H) S (= O) ₂ -R ', in which each sulfur atom belongs to a sulfonyl group, where each one is linked to two oxygen atoms through double bonds, through single bonds to the corresponding R chain and both bound to the same nitrogen atom of the central amine.

In a similar way to sulfinamides, this type of chemical substances are used in enantioselective synthesis processes (also known as asymmetric synthesis) due to their catalysis function.

Other sulfonamides

This classification of sulfonamides is not governed by the previous one, but they are cataloged from the pharmaceutical point of view into: pediatric antibacterial drugs, antimicrobials, sulfonylureas (oral antidiabetics), diuretic agents, anticonvulsants, dermatological drugs, antiretrovirals, antivirals against hepatitis C, among others.

It should be noted that among antimicrobial drugs there is a subdivision that classifies sulfonamides according to the speed with which they are absorbed by the body

Examples

There are a huge number of sulfonamides that can be found commercially. Some examples of these are described below:

Sulfadiazine

It is widely used for its antibiotic activity, acting as an inhibitor of the enzyme called dihydropteroate synthetase. It is very commonly used in conjunction with pyrimethamine in the treatment of toxoplasmosis.

Chloropropamide

It is part of the group of sulfonylureas, having the function of increasing the production of insulin for the treatment of type 2 diabetes mellitus. However, its use has been discontinued due to its side effects.

Furosemide

It belongs to the group of diuretics and shows various reaction mechanisms, such as interference in the ion exchange process of a specific protein and the inhibition of certain enzymes in certain activities of the body. It is used to treat edema, hypertension and even congestive heart failure.

Brinzolamide

The enzyme called carbonic anhydrase, which is located in tissues and cells such as red blood cells, is used in the inhibition. It works in the treatment of conditions such as ocular hypertension and open-angle glaucoma.

References

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4. ScienceDirect. (sf). Sulfonamide. Retrieved from sciencedirect.com
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