Biological Activities of Pyridine Derivatives

Pyridine is a unique nitrogen-containing aromatic ring compound. Besides being widely used in industry, pyridine is also present in many natural products such as vitamins, coenzymes and alkaloids. Pyridine compounds are often used in medicine due to their basicity, water solubility, stability, hydrogen bond formation ability and small molecular size. In addition, the substitution of pyridine rings plays an important role in drug discovery because pyridine rings can act as bioisomers of amines, amides, nitrogen-containing heterocycles, and benzene rings.

Pyridine has a wide range of pharmacological activities, including antibacterial, antiviral, antioxidant, antidiabetic, antimalarial, anti-inflammatory, psychopharmacological antagonists and anti-amoeba agents. Although many pyridine-containing drugs and pesticides are designed to improve water solubility, this improvement usually depends on pH. For example, the sulfonamide drug sulfapyridine has good antibacterial activity and water solubility under acidic conditions, but there is a risk of bladder or urethral crystallization, resulting in urethral pain or blockage. In this article we will summarize the various biological activities of pyridine and its derivatives.

• Anti-microbial

Compared with the standard drug streptomycin sulfate, pyridine derivatives such as diacylhydrazine (Compound 1) and acyl(arylsulfonyl)hydrazine (Compound 2) have exciting antibacterial activity against the gram-negative bacteria Escherichia coli and the gram-positive bacteria Candida albicans. They have also been tested as herbicides for the control of C. rotundus, E. crusgalli, E. hirta, E. indica and T. procumbens. In addition, thienopyridine compounds have good antibacterial activity against Gram-positive bacteria and Staphylococcus aureus, and are also effective against Gram-negative Escherichia coli, Pseudomonas aeruginosa, and Pseudomonas vulgaris.

Fig. 1. Structural representation of compound 1 and 2.

• Anti-viral

Oxime derivatives of thiazolo[5,4-b]pyridine are active against influenza B virus. However, oxime derivatives of pyridine and naphthyridine are highly active against HIV. It has recently been reported that naphthyridine oximes also exhibit antibacterial activity and are used in drug discovery research. In addition, pyridine and derivatives have broad anti-viral (HCV) capabilities. For example, the hydrohydrazones of 3-acetylpyridine and 4-acetylpyridine with antitumor activities can also inhibit the replication of HCV both RNA(+) and RNA(-) chains. And bipyridine derivatives complexed with ruthenium have antiviral activity against hepatitis C virus (HCV).

• Antioxidant

In addition to cytotoxic activity, some thiopyridine derivatives also have antioxidant effects, which are very attractive, especially compound 3 shows the highest antioxidant and cytotoxicity. Generally, antioxidant and cytotoxic activities are closely related to the structure of the compounds. Studies have shown that dipole moment and electrophilic index are the most important descriptors that correlate the molecular structure of compounds with their respective antioxidant activities. The results showed that the molecules with high dipole moment and electrophilic index also had higher antioxidant activity. However, those compounds with the lowest atomic polarizability have the highest cytotoxic activity.

Fig. 2. Representative example of antioxidant.

• Anti-Diabetic

In addition, several studies have reported antidiabetic activity of pyridine derivatives containing thiazolidinone. For example, some of these compounds showed very potent anti-diabetic activity, while others showed significant anti-diabetic effects, and these findings may facilitate the development of new anti-diabetic drugs in the future.

• Anti-Cancer Activities

When pyrazoline, pyridine and pyrimidine are coupled with indole functional groups, the obtained products have excellent antitumor activity. For example, 2-acetylpyridine derivatives and 2-benzoxazolylhydrazon also have good antitumor activity. If the acetyl group is replaced by an acyl group, it has a good inhibitory effect on leukemia, colon cancer and ovarian cancer cell lines. In addition, several studies have shown that pyridine derivatives also exhibit excellent antitumor activity when they form complexes with metals. For example, the palladium and zinc complexes of 2-acetyl pyridine thiosemicarbazone have good antitumor activity against human cells with less cytotoxicity, and are potential candidates for future antitumor drugs.

• Anti-Amoebic Agents

Some acetylpyridine-derived ligands have anti-amebic activity, however, the anti-amoeba activity increases dramatically when the ligand is coupled with ruthenium (II) to form a complex. Compared with the commercially available standard drug metronidazole, compound 4 showed higher anti-amoeba activity. In addition, the vanadium binuclear complex containing 2-acetylpyridine exhibited excellent amebicicidal activity with IC₅₀ values of 1.68-0.40, followed by the commercial drug methazole with IC₅₀ value of 1.81.

Fig. 3. Ruthenium complex as anti-amoebic agent.

In addition to the above pharmacological activities, pyridine and its derivatives can be used as basic structural units of antimalarial, anti-inflammatory and analgesic drugs. Some pyridine compounds also have antagonistic psychopharmacological and enzyme inhibitory effects. Click here to learn about our pyridine products.

Reference

1. Altaf, A.A. et al. A review on the medicinal importance of pyridine derivatives. J. Drug Des. Med. Chem. 2015, 1(1): 1-11.