ALKALOIDS: STRUCTURE, BIOSYNTHESIS, CLASSIFICATION AND USES - BIOLOGY - 2025

The alkaloids are molecules containing carbon and nitrogen atoms in its molecular structure, which generally form complexes rings. The term alkaloid, which was first proposed by the pharmacist W. Meissner in 1819, means "similar to alkali."

The word alkali refers to the ability of a molecule to absorb hydrogen ions (protons) from an acid. Alkaloids are found as individual molecules, so they are small and can absorb hydrogen ions, turning them into a base.

Biosynthesis of alkaloids

Some common bases include milk, calcium carbonate in antacids, or ammonia in cleaning products. Alkaloids are produced by some living things, particularly plants. However, the role of these molecules in plants is not clear.

Regardless of their role in plants, many alkaloids have uses in medicine for humans. Pain relievers derived from the poppy plant, such as morphine, have been around since 1805. Another example is the antimalarial quinine, which has been used by tribes in the Amazon for more than 400 years.

Papaver somniferum, or poppy plant

Structure

The chemical structures of alkaloids are extremely variable. Generally, an alkaloid contains at least one nitrogen atom in an amine-like structure; that is, a derivative of ammonia by replacing hydrogen atoms with hydrogen-carbon groups called hydrocarbons.

This or another nitrogen atom can be active as a base in acid-base reactions. The name alkaloid was originally applied to these substances because, like inorganic alkalis, they react with acids to form salts.

Most alkaloids have one or more of their nitrogen atoms as part of a ring of atoms, often called a ring system. Alkaloid names generally end in the suffix "-ina", a reference to their chemical classification as amines.

Biosynthesis

The biosynthesis of alkaloids in plants involves many metabolic steps, catalyzed by enzymes belonging to a wide range of protein families; for this reason, the alkaloid biosynthesis pathways is considerably complex.

However, it is possible to comment on some generalities. There are a few major branches in alkaloid synthesis including:

Biosynthesis of tropan and nicotinic alkaloids

In this group of alkaloids, biosynthesis is carried out from the compounds L-Arginine and Ornithine. These undergo a decarboxylation process mediated by their respective enzymes: arginine decarboxylase and ornithine decarboxylase.

The product of these reactions are putrecine molecules. After other steps, including the transfer of methyl groups, the nicotinic derivatives (such as nicotine) and tropan derivatives (such as atropine and scopolamine) are produced.

Biosynthesis of benzylisoquinoline alkaloids

The synthesis of benzyl isoquinoline alkaloids begins from L-tyrosine molecules, which are decarboxylated by the enzyme tyrosine decarboxylase to give rise to tyramine molecules.

The enzyme norcoclaurin synthase uses the tyramine produced in the previous step and L-DOPA to form norcoclaurin molecules; they undergo another series of complex reactions to give rise to the alkaloids berberine, morphine and codeine.

Biosynthesis of terpenic indole alkaloids

This group of alkaloids is synthesized from two routes: one that starts from L-tryptophan and another from geraniol. The products of these routes are tryptamine and secolaganine, these molecules are the substrate for the enzyme strectosidine synthase, which catalyzes the synthesis of strictosidine.

The different terpenic indole alkaloids are produced from strectosidine, such as ajmalicine, catarantine, serpentine and vinblastine; the latter has been used in the treatment of Hodgkin's disease.

In the fields of structural biochemistry, molecular and cellular biology, and biotechnological applications, the characterization of new alkaloid biosynthetic enzymes has been the focus of research in recent years.

Classification

Due to their diversity and structural complexity, alkaloids can be classified in different ways:

According to its biosynthetic origin

According to their biosynthetic origin, alkaloids are classified into three large groups:

True alkaloids

They are those that are derived from amino acids and have the nitrogen atom as part of the heterocyclic ring. For example: hygrine, cocaine and physostigmine.

Protoalkaloids

They are also derived from amino acids, but nitrogen is not part of the heterocyclic ring. For example: ephedrine and colchicine.

Pseudoalkaloids

They are alkaloids that do not derive from amino acids and nitrogen is part of the heterocyclic structure. For example: aconitine (terpene alkaloid) and solanidine (steroidal alkaloid).

According to its biogenetic precursor

In this classification alkaloids are grouped depending on the molecule from which their synthesis starts. Thus, there are the alkaloids derived from:

- L-Phenylalanine.

- L-Tyrosine.

- L-Tryptophan.

- L-Ornithine.

- L-Lysine.

- L-Histidine.

- Nicotinic acid.

- Anthranilic acid.

- Purple bases.

- Terpenic metabolism.

According to its chemical structure or basic nucleus

- Pyrrolidine.

- Pyridine-Pyrrolidine.

- Isoquinoline.

- Imidazole.

- Piperidine.

- Pyridine-Piperidine.

- Quinoline.

- Purina.

- Tropane.

- Indole .

Applications

Alkaloids have multiple uses and applications, both in nature and in society. In medicine, the use of alkaloids is based on the physiological effects they cause in the body, which is a measure of the toxicity of the compound.

Being organic molecules produced by living beings, alkaloids have the structural ability to interact with biological systems and directly affect the physiology of an organism. This property may seem dangerous, but the use of alkaloids in a controlled way is very useful.

Despite their toxicity, some alkaloids are helpful when used in the correct doses. An excess dose could cause damage and be considered poisonous to the body.

The alkaloids are obtained mainly from shrubs and herbs. They can be found in different parts of the plant, such as leaves, stem, roots, etc.

Alkaloids can be used as medicines

Some alkaloids have significant pharmacological activity. These physiological effects make them valuable as medicines to cure some serious disorders.

For example: Vincristine from Vinca roseus is used as an anticancer drug, and ephedrine from Ephedra distachya is used to regulate blood pressure.

Other examples include curarina, which is found in curare and is a powerful muscle relaxant; atropine, which is used to dilate the pupils; codeine, which is used as a cough suppressant; and ergot alkaloids, which are used to relieve migraine headaches, among many others.

Alkaloids can be used as narcotics

Many psychotropic substances, which act on the central nervous system, are alkaloids. For example, morphine from opium (Papaver somniferum) is considered a drug and a pain reliever. Lysergic acid diethylamide, better known as LSD, is an alkaloid and a psychedelic drug.

These narcotics have been used since ancient times as instruments for mental excitement and euphoria, although they are considered harmful according to modern medicine.

Alkaloids can be used as pesticides and repellants

Most of the natural pesticides and repellants are derived from plants, where they exert their function as part of the plant's own defense system against the insects, fungi or bacteria that affect them. These compounds are generally alkaloids.

As mentioned above, these alkaloids are toxic in nature, although this property is highly concentration dependent.

For example, pyrethrin is used as an insect repellent, at a concentration that is deadly to mosquitoes but not to humans.

Alkaloids can be used in scientific research

Due to their specific effects on the body, alkaloids are widely used in scientific studies. For example, the alkaloid atropine can cause the pupil to dilate.

So, to evaluate whether a new substance has similar or opposite effects, it is compared to the effect of atropine.

Some alkaloids are studied with great interest due to their antitumor properties, such as vinblastine and vincristine.

Other important alkaloids in scientific research include quinine, codeine, nicotine, morphine, scopolamine, and reserpine, among others.

References

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