Cycloserine | Antibiotic | CAS 68-41-7 | Tuberculosis Treatment

Product Name: Cycloserine
CAS No.: 68-41-7
Chemical Name: (R)-4-aminoisoxazolidin-3-one
Molecular Formula: C₃H₆N₂O₂
Appearance: White to pale yellow crystalline powder, hygroscopic
Solubility: Freely soluble in water
Stability: Unstable in acidic environments; aqueous solutions decompose upon heating

1. Introduction

Cycloserine is a broad-spectrum antibiotic and a structural analog of D-alanine. It disrupts bacterial cell wall synthesis. It is used as a second-line anti-tuberculosis agent, particularly for the treatment of multidrug-resistant tuberculosis.

Cycloserine was isolated from the culture of Streptomyces orchidaceus and can also be produced synthetically. It has a broad spectrum of antibacterial activity, but its main clinical application is the treatment of tuberculosis caused by Mycobacterium tuberculosis strains resistant to first-line drugs. Due to potential neurotoxicity, its use requires caution and careful monitoring.

2. Chemical Structure & Synthesis

Cycloserine is a cyclic analog of the amino acid D-alanine.

Synthesis: Can be obtained both by fermentation and fully synthetically. One synthetic approach involves the cyclization of hydroxylamine derivatives with α-halopropionic acid derivatives.

3. Mechanism of Action

Cycloserine is a competitive inhibitor of two enzymes involved in bacterial cell wall peptidoglycan synthesis:

• Alanine racemase – catalyzes the conversion of L-alanine to D-alanine

• D-alanyl-D-alanine synthetase (Ddl) – catalyzes the formation of the D-alanyl-D-alanine dipeptide

Disruption of these steps leads to inhibition of peptidoglycan synthesis, weakening of the cell wall, and subsequent lysis of the bacterial cell (bactericidal action).

4. Antimicrobial Spectrum

Active against:

• Mycobacterium tuberculosis

• Some other Gram-positive and Gram-negative bacteria (e.g., Enterococcus spp., Escherichia coli)

5. Pharmacokinetics

Well and rapidly absorbed after oral administration. Widely distributed in tissues and body fluids, including cerebrospinal fluid (even in non-inflamed meninges). Partially metabolized. Excreted primarily by the kidneys.

6. Applications

• Treatment of active pulmonary and extrapulmonary tuberculosis – in combination with other anti-tuberculosis drugs, especially in the presence of resistance to first-line drugs (e.g., multidrug-resistant tuberculosis – MDR-TB)

• Urinary tract infections – caused by sensitive bacterial strains when other antibiotics are ineffective or cannot be used (rarely)

7. Conclusion

Cycloserine is an important component of treatment regimens for drug-resistant tuberculosis. Its unique mechanism of action, targeting cell wall synthesis, makes it effective against Mycobacterium tuberculosis. However, its use is limited by the risk of serious central nervous system side effects (seizures, psychosis, depression, headaches), requiring careful patient monitoring and frequent co-administration of pyridoxine to reduce neurotoxicity.