(367) Synthesis and Antimicrobial Evaluation of A Novel Puromycin Analog

Trainee Category: Student Pharmacist

Objective :

Objective: To synthesize a novel puromycin analog lacking the nephrotoxic effects of the parent compound, and to evaluate its antimicrobial activity against selected Gram-positive and Gram-negative microorganisms.

Methods:

Methods: The target molecule was synthesized from a carbohydrate precursor by a 10-step stereo- and regioselective procedure. All intermediates were fully characterized, and their stereochemistry was confirmed through spectroscopic methods. Antimicrobial activity was measured by minimum inhibitory concentration and minimum bactericidal concentration assay against multidrug-resistant Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa.

Results:

Results: The target molecule was designed based on previous analogs that showed antimicrobial activity comparable to puromycin, but low chemical stability. All analogs lack the functional group associated with the nephrotoxicity of puromycin. The target molecule showed equal or greater antimicrobial activity compared to puromycin in all tested strains.

Conclusions:

Conclusions: We synthesized a chemically stable puromycin analog with antimicrobial activity comparable to the parent molecule, but without the ability to generate puromycin aminonucleoside, the nephrotoxic metabolite of puromycin. This optimized lead expands the known structure-activity relationships of puromycin and has the potential to be further developed and lead to the discovery of new effective antimicrobials.