Chloramphenicol: Chemical Structure, Mechanism of Action, Uses & Side effects

Chemical formula:

• C11H12Cl2N2O5

Structure of Chloramphenicol

Mechanism of action:

• Chloramphenicol works by inhibiting bacterial protein synthesis.

• It binds to the 50S subunit of the bacterial ribosome and prevents the formation of peptide bonds between amino acids, thereby blocking the elongation of the growing polypeptide chain.

• This ultimately leads to the inhibition of bacterial growth and the death of the bacteria.

Structure-Activity Relationship (SAR):

• The nitro group (NO2) on the benzene ring is essential for the antibacterial activity of chloramphenicol. The nitro group is thought to interfere with bacterial protein synthesis.

• The dichloroacetamide moiety is a crucial part of the chloramphenicol structure. Alteration or removal of this group results in loss of antibacterial activity.

• The molecule's chirality also plays a role in its activity. The D-threo isomer is the active form of the drug, while the L-threo isomer is inactive.

• The hydroxyl group is involved in hydrogen bonding with the bacterial ribosome, so it is also crucial for activity.

Synthesis:

• Chloramphenicol is usually synthesized starting from dichloroacetic acid and p-nitroacetophenone.

• The reaction involves a condensation to form an α-keto ester, followed by a reduction to remove the nitro group.

• Step (1) Cl2CHCOOH + C6H5C(=O)CH3 → Cl2CHCOOC(=O)C6H5 + H2O

• Step (2) Cl2CHCOOC(=O)C6H5 + 3 H2 → Cl2CHCOOHC6H4NH2

• The first step is a condensation reaction between dichloroacetic acid and p-nitroacetophenone, while the second step is a reduction of the nitro group to an amine.

Uses:

• Chloramphenicol is used to treat a wide range of bacterial infections, including typhoid fever, meningitis, respiratory tract infections, and skin and soft tissue infections.

• It is also used as a second-line treatment for certain infections, such as those caused by drug-resistant strains of bacteria.

Side effects:

• Chloramphenicol is associated with several side effects, including bone marrow suppression, which can lead to anaemia, leukopenia, and thrombocytopenia.

• It can also cause gastrointestinal disturbances, such as nausea, vomiting, and diarrhea, as well as allergic reactions, including skin rashes and anaphylaxis.

• In rare cases, chloramphenicol can cause a serious condition called Gray baby syndrome in new-borns, which can be fatal.