Heterocyclic compounds and their biological significance

1. PRESENTED BY
KUSUMA M
I M.SC BIOCHEMISTRY
JAIN UNIVERSITY (SCHOOL OF
SCIENCES)

2. DEFINITION
Incorporation of an oxygen, a nitrogen, a sulfur, or an atom of a related
element into an organic ring structure in place of a carbon atom gives rise to a
heterocyclic compound.
In other words, heterocyclic compounds are organic compounds that contain
one or more heteroatoms i.e., nitrogen, sulfur, oxygen in the ring structure.
Heterocyclic compounds can be classified based on their electronic structure.

4. PYRIDINE
Chemical Formula : C5H5N
PYRIDINE is a six-membered ring structure composed of five carbon atoms and
one nitrogen atom.
Pyridine was isolated and characterized by Anderson in 1846, it was obtained
from bone oil and coal tar.
Pyridine is a clear colorless to light yellow liquid with a penetrating nauseating
odor.

5. BIOLOGICAL SIGNIFICANCE
Exhibits antiviral, anticancer, antimicrobial, antidiabetic, antidote, antileishmanial,
antioxidant, antithrombin, anticoagulant and Precursors to agrochemicals.
It occurs in azines and the vitamins niacin (Vitamin B3) and pyridoxine (Vitamin
B6).
It acts as prosthetic groups : Coenzymes of Dehydrogenases (NADP+ and
NAD+), acts as oxidant.
Pyridine and their derivatives are active against microbial diseased, viral
problems and variety of cancerous cells - by interacting with enzymes, proteins
and DNA.

6. BIOLOGICAL ACTIVITIES OF PYRIDINE DERIVATIVES
ANTIVIRAL ACTIVITY
4-(phenylamino)thieno[2, 3-b] pyridine derivative shows inhibitory activity against
Herpes simplex virus type-1 (HSV-1). [1]
The 1-(β-D-ribofuranosyl)-pyridine-2-thiones are found to be most active anti-HIV
agents. [1]

7. ANTICANCER ACTIVITY
Pyridine epothilones-couple with metals exhibit cytotoxic properties. [1]
ANTIMICROBIAL ACTIVITY
Schiff base ligands of type 1-phenyl-2,3-dimethyl-4-salicylalidene pyrazole-5-one, couple
with metal center such as Cu2+, Ni2+, Zn2+ and Fe3+ - exhibit antibacterial and antifungal
activities.
3-hydroxypyridine-4-ones and 3-hydroxy-pyran-4-ones containing pyridine ring
are active against Staphylococcus aureus, Aspergilus niger and Candida
albicans. [1]

8. OTHER APPLICATIONS
PESTICIDES
• Precursor to the herbicides paraquat and diquat.
• It is the starting compound for the preparation of pyrithione-based fungicides.
ANTISEPTIC
• Cetylpyridinium and laurylpyridinium, are used as antiseptic in oral and dental care
products.
SOLVENT
• Pyridine is used as a solvent in the manufacture of dyes and rubber.
• It is also used in the textile industry to improve network capacity of cotton.
• Pyridine is added to ethanol to make it unsuitable for consumption.
• In low doses - added to foods to give them a bitter flavor - approved by the US Food
and Drug Administration.

9. HEALTH ISSUES
The lowest known lethal dose for the ingestion of pyridine in humans is 500
mg.kg−1. In high doses, pyridine has a narcotic effect.
Pyridine is harmful if inhaled, swallowed or absorbed through the skin.
Effects of acute pyridine intoxication include
• Dizziness
• Headache
• lack of coordination
• Nausea
• Salivation
• loss of appetite.

11. PYRIMIDINE
Chemical Formula : C4H4N2
Pyrimidines are simple aromatic, six-membered ring compound.
The carbon and nitrogen atoms are connected via alternating double and single
bonds, making the structure resonance stable.
The modifications of its derivatives can range from addition of a few atoms in
nucleic acids to complex structures in drugs and vitamins.

12. BIOLOGICAL SIGNIFICANCE
The three pyrimidine nitrogenous bases, act as the genetic material in all living
organisms.
Pyrimidine activated sugars are also involved in
• polysaccharide and phospholipid synthesis,
• glucuronidation in detoxification processes,
• glycosylation of proteins and lipids.
The pyrimidine derivative, neurotoxin tetrodotoxin found in Japanese puffer fish,
the blue-ringed octopus, prevents the transmission of nerve signals and can result
in paralysis and death.
Found in vitamins like, riboflavin, thiamine and folic acid.

13. BIOLOGICAL ACTIVITIES OF PYRIMIDINE
DERIVATIVES
Pyrimidine is present in barbituric acid and its several derivatives e.g. Veranal
which are used as hypnotics.
DRUGS FOR HYPERTHYROIDISM:
2-Thiouracil and its alkyl analogue, thiobarbital and Propylthiouracil
are effective drugs against hyperthyroidism. [2]
ANTHELMENTICS:
Pyrantel pamoate is a depolarizing neuromuscular blocking agent that is
employed in the treatment of infestations caused by pinworms and roundworms. [2]

15. PURINES
Purine is an aromatic heterocyclic compound with two cycles: a six-membered
pyrimidine ring and a five-membered imidazole ring fused together.
Building blocks of all living things. In the human body, purines can be divided
into two categories:
• Exogenous purines that enter the body via food. It includes meat, certain
vegetables like asparagus, spinach, mushrooms, carrots and tomatoes in
varying concentrations.

16. • Endogenous purines that are synthesized by the body.
Examples: DNA and RNA (containing the purines adenine and
guanine), ATP, ADP, AMP, cyclic AMP, GTP and cGMP
GTP

17. BIOLOGICAL SIGNIFICANCE
Purines are critical elements of the energy metabolism molecules:
reduced nicotinamide adenine dinucleotide, nicotinamide adenine
dinucleotide phosphate (NADPH), and coenzyme Q.
Purines may also serve as direct neurotransmitters; for example,
adenosine.

18. BIOLOGICAL ACTIVITIES OF PURINE
ANALOGUES
ANTI-LEISHMANIAL ACTIVITY
Purine and its derivatives have cytotoxic activity and anti-leishmanial activity on Human
epidermoid carcinoma and Vero (African green monkey kidney) cells. [3]
ANTITUMOR ACTIVITY
Some derivatives of L-Ascorbic acid inhibit the growth of certain human malignant
tumor cell lines. [3]
ANTIPROTOZOAL ACTIVITY
Natural products having a hybrid terpene-purine from numerous genera of sponges
display high general toxicity towards protozoa. [3]

19. ROLE OF PURINES IN GOUT
Purines are substances in animal and plant foods that your body converts to
uric acid.
Too much uric acid in your body causes gout.
If uric acid cannot be flushed out through your kidneys, it can build up in the
bloodstream and be deposited as needle-shaped crystals in your joints,
causing severe inflammation and intense pain of a gout attack.

21. QUININE
Chemical Formula : C20H24N2O2
Quinine is a natural white crystalline alkaloid derived from the bark of the
cinchona tree. It is a stereoisomer of quinidine.
Quinine is found to have antipyretic, anti-malarial with analgesic and anti-
inflammatory properties.

22. BIOLOGICAL SIGNIFICANCE
TREATMENT OF MALARIA
• Quinine is used parenterally to treat life-threatening infections caused
by chloroquine-resistant Plasmodium falciparum malaria.
• Malaria in pregnancy causes several adverse outcomes.
• The combination of quinine and clindamycin has efficacy against
multidrug-resistant strains of P. falciparum.
MODE OF ACTION
It is thought to act by inhibiting heme polymerase, thereby allowing
accumulation of its cytotoxic substrate, heme.

23. OTHER MEDICAL USES
Used for idiopathic muscle cramps.
Induces uterine contractions during childbirth.
NON MEDICINAL USES
In small amounts, quinine is a component of various drinks,
• ingredient of tonic drinks, acting as a bittering agent.
• flavor component of bitter lemon, and vermouth.
Quinine is often added to street drugs cocaine or ketamine in
order to "cut" the product and make more profit.
It is also used in photochemistry as a common fluorescence
standards.

24. SIDE EFFECTS OF QUININE
• Acute hypersensitivity reactions to quinine that include hepatic
involvement.
• Cinchonism or quinism is a pathological condition in humans caused by
an overdose of quinine or its natural source, cinchona bark.
• Quinine can cause paralysis if accidentally injected into a nerve. It is
extremely toxic in overdose.

26. PTERIDINES
Pteridines belong to a class of nitrogen heterocyclic compound, consists of
pyrazine and pyrimidine ring.
Found in natural materials as pigments in the wings and eyes of insects, and
in the skin of fish, amphibia and reptiles.

27. BIOLOGICAL SIGNIFICANCE
Two important coenzymes are derived from pteridine:
• Pterin coenzyme
• Folic acid
PTERIN COENZYME
In eukaryotes, pterins play a role of redox cofactors.
Pterins also play biological roles in mediating process like protection from UV
damage and intercellular signaling.
In cyanobacteria Spirulina platensis, biopterin glucoside protect the components of
photosynthetic vesicles (chlorophyll a, phycocyanin and carotenoids) from UV
exposure.

28. FOLIC ACID
It is pteroylglutamic acid, consists of pteridine portion linked through p-benzoic acid
to L-glutamic acid.
Found in animal tissues and human red cells as a polyglutamate.
Tetrahydrofoliate (THF)-active form - synthesis depends on Vitamin C and NADPH.
The major functions of foliate co-enzymes is one carbon metabolism. THF is
required in cell division, lowering plasma homocysteine.

29. One-carbon groups are being added to or removed from THF and are changing
their nature while bound to THF.
Folic acid deficiency leads to,
• Megaloblastic anaemia
• Neural tube defects in fetus
• Hyperhomocysteinemia

31. ISOALLOXAZINE
Chemical Formula : C10H6N4O2
The 2, 4-dioxoderivative of benzopteridine.
A yellow solid that is the precursor of various
flavins (such as riboflavin).
Riboflavin is part of coenzymes FAD and FMN.

32. FLAVIN COENZYMES
Commonly known as Vitamin B2. Its coenzyme forms are Flavin
mononucleotide (FMN) and Flavin adenine dinucleotide (FAD)
FAD and FMN act as intermediate Hydrogen acceptors in the
mitochondrial ETC.
Deficiency is often seen in chronic alcoholics due to their poor dietetic
habits.
Symptoms include glossitis, seborrhea, angular stomatitis.

33. BIOLOGICAL SIGNIFICANCE
The flavoproteins act as
• Oxidases
• Dehydrogenases
• Hydroxylases
• Oxidative carboxylases
Riboflavin and its coenzymes are involved in
• Growth and Tissue respiration
• Light adaption
• Conversion of pyridoxine to pyridoxal phosphate
• Cellular metabolism
• Enzymatic oxidation of glucose, amino acids, fatty acids, purines etc.

34. Riboflavin or Vitamin B2- required for red blood cell formation, antibody production
and regulating human growth and reproduction.
Aids in Beta oxidation in fat metabolism.
Neutralizes the free radicals in body and
help prevent heart disease and cancer.
Effective in treatment of
• Ariboflavinosis
• Migraine headaches
• Cataracts
• Rheumatoid arthritis
• Dermatitis
• Eczema
• Anemia
• Alzheimer’s disease
• Epilepsy

35. REFERENCES
1. Pyridine : A Versatile Nucleuse In Pharmaceutical Field, Ajit Chaubey, S.N.
Pandeya, Department of Pharmaceutical Sciences, Saroj Institute of Technology
and Management.
2. An Overview on Synthesis and Biological Activity of Pyrimidines, N.
Venkat Rao, Bhanu Vaisalini. N, B. Mounika, Lakshmi Harika. V, Pasanna Kumar
Desu, Sreekanth Nama,
Department of Pharmaceutical Sciences, PIPER.
3. Biological Activities of Purine Analogues: A Review, Sachan Dinesh,
Gangwar Shikha, Gangwar Bhavana, Sharma Nidhi, Sharma Dileep.
http://www.newworldencyclopedia.org/entry/Quinine
https://pubchem.ncbi.nlm.nih.gov
https://www.researchgate.net/publication/