Stable Tricyclic Antitubercular Ozonides Derived from Artemisinin

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Infectious Diseases

Background:

• Tuberculosis (TB) remains a major global health challenge, necessitating the development of novel therapeutic agents.
• Artemisinin derivatives have shown potential in various therapeutic areas, including antimicrobial applications.

Purpose of the Study:

• To synthesize and characterize novel, stable tricyclic ozonides derived from artemisinin.
• To evaluate the antitubercular activity of these new compounds against Mycobacterium tuberculosis.

Main Methods:

• Synthesis of tricyclic ozonides 9 and 10 from artemisinin.
• Stability testing of ozonides under acidic and basic conditions.
• Determination of the absolute configuration of ozonide 9 via X-ray crystallography.
• Antitubercular activity testing of ozonide 10 against M. tuberculosis H37Ra and M. tuberculosis H37Rv using MIC assays.

Main Results:

• Two new, highly stable tricyclic antitubercular ozonides, 9 and 10, were synthesized in 39% and 9% yields, respectively.
• The ozonide functionalities in compounds 9 and 10 demonstrated stability under harsh basic and acidic conditions.
• The absolute configuration of ozonide 9 was unequivocally confirmed through X-ray crystallographic analysis.
• Ozonide 10 displayed potent antitubercular activity, with minimum inhibitory concentrations (MICs) of 0.39 μg/mL against M. tuberculosis H37Ra and 3.12 μg/mL against M. tuberculosis H37Rv.

Conclusions:

• Novel, stable tricyclic ozonides derived from artemisinin have been successfully synthesized.
• Ozonide 10 exhibits significant in vitro activity against clinically relevant strains of Mycobacterium tuberculosis.
• These findings highlight the potential of these novel ozonides as leads for developing new antitubercular drugs.