• Good day we are the group 4 and this is the recording of our prelim project in Pharmaceutical Organic

Medicinal Chemistry. The drug that we chose that acts on nucleic acids is rifampicin which will be
discussed later on by the other members. First, let’s have a brief discussion about rifampin, the group
where rifampicin belongs.

• Rifampin (Rifadin, Rimactane, Rifampicin) is the most active drug in clinical use against tuberculosis.
Against sensitive strains of M. tuberculosis, a dose of as little as 5 microliter/mL is effective. Rifampin is
also effective against staphylococci, Neisseria gonorrhoeae, Haemophilus influenzae, Legionella
pneumoniae, and Chlamydia species. Rifampin sensitivity is substantially lower in Gram-negative
bacteria. Rifampin resistance develops quickly in most bacteria species, including the tubercle bacillus.
As a result, rifampin is typically only prescribed in combination with other antitubercular medications,
and it is rarely prescribed for the treatment of other bacterial infections when other antibacterial treatments
are available.

• Rifampin is a crystalline powder that ranges from orange to reddish brown in color and is soluble in
alcohol but only in sparingly soluble in water. It is moisture-resistant and acts as a desiccant. Rifampin
capsule containers should comprise (silica gel). Capsules stored in this manner have a two-year expiration
date. After oral treatment, rifampin is well absorbed and provides effective blood levels for around 8
hours. Food, on the other hand, significantly lowers rifampin's oral absorption. It's best to take it on an
empty stomach. Despite the fact that it is 70% to 80% protein bound in the plasma, it is distributed in
effective amounts to all body fluids and tissues except the brain.

• Rifampin is also available as a lyophilized sterile powder that, when reconstituted in 5% dextrose or
normal saline, yields 600 mg of active medication in 10 mL for slow IV infusion. The parenteral form
can be utilized to treat serious illnesses as well as for patients who are unable to take the medication. The
medication is taken orally. Rifampin parenteral solutions are stable at room temperature for 24 hours.
Although rifampin is stable in the solid state, it undergoes a variety of chemical changes in solution, the
rates and nature of which are affected by pH and temperature. In the presence of oxygen, it oxidizes to a
quinone at alkaline pH; in acidic conditions, it hydrolyzes to 3-formyl rifamycin SV.

• The main excretory organ routes is through the bile and feces with large concentrations of rifampin and
its major metabolite, deacetylrifampin, are found in the liver and biliary system. Deacetylrifampin has
biological activity as well. Rifampin is found in high concentrations in the kidneys, and while a significant
amount of the drug is passively reabsorbed in the renal tubules, urinary excretion is significant. Rifampin
causes a reddish orange discoloration of the urine, stool, saliva, tears, and skin, which should be informed
to patients. It can also discolor soft contact lenses permanently.

• Rifampin is a potent inducer of cytochrome P450 oxygenases in the liver. It has the ability to significantly
enhance the effects of medications that are inactivated by these enzymes. Hepatic dysfunction is a
condition in which the liver's function is impaired (e.g., chronic alcoholics) People with liver disease
should not use it or in combination with other potentially hepatotoxic medications.

• One example of rifampin is rifampicin. Rifampicin acts via the inhibition of DNA-dependent RNA
polymerase, leading to a suppression of RNA synthesis and cell death.
• Rifampicin is a bactericidal antibiotic used to treat tuberculosis and penicillin-resistant staphylococci
infections. It can be used to cure leprosy when combined with dapsone, and also to treat brucellosis,
legionnaires' disease, and other infections. When treating tuberculosis in AIDS patients, this presents a
significant challenge as it boosts the activity of the cytochrome P450 enzyme family (CYP3A) in patients.
These enzymes break down HIV protease inhibitors, which are used in HIV treatment, reducing their
effectiveness. Also reduces the effect of oral anticoagulants, oral contraceptives, and barbiturates.

• Rifampicin is a semi-synthetic rifamycin that is derived from an antibiotic discovered in 1957 in

Streptomyces mediterranei. It operates by binding non-covalently to DNA-dependent RNA polymerase
 and blocking the onset of RNA synthesis in Gram-positive bacteria. Because the medication binds to a
peptide chain not seen in mammalian RNA polymerases, eukaryotic cells are unaffected.

• Furthermore, resistance to rifampicin in E. coli arises from mutations in the rpoB gene which cause amino
acid changes or minor deletions in a specific area of the beta-subunit of RNA polymerase (Jin & Gross,
1988, 1989). Mutation leads to formation of an RNA chain beyond 2 or 3 nucleotides, according to
structural and molecular research. Because RNA in the exit channel limits rifampicin binding, elongating
RNA polyphryase is unaffected by inhibition. As a result, after the addition of rifampicin, runoff
transcription continues.

RED – de Vera
GREEN – Asenjo
BLUE – Eduave
PURPLE – De Villa