Improving the Antimycobacterial Drug Clofazimine through Formation of Organic Salts by Combination with Fluoroquinolones

与氟喹诺酮类药物联合形成有机盐改进抗分枝杆菌药物氯法齐明

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作者:Clara M Bento, Ana Teresa Silva, Bruno Mansano, Luísa Aguiar, Cátia Teixeira, Maria Salomé Gomes, Paula Gomes, Tânia Silva, Ricardo Ferraz

Abstract

This work reports the synthesis, structural and thermal analysis, and in vitro evaluation of the antimicrobial activity of two new organic salts (OSs) derived from the antimycobacterial drug clofazimine and the fluoroquinolones ofloxacin or norfloxacin. Organic salts derived from active pharmaceutical ingredients (API-OSs), as those herein disclosed, hold promise as cost-effective formulations with improved features over their parent drugs, thus enabling the mitigation of some of their shortcomings. For instance, in the specific case of clofazimine, its poor solubility severely limits its bioavailability. As compared to clofazimine, the clofazimine-derived OSs now reported have improved solubility and thermostability, without any major deleterious effects on the drug's bioactivity profile.

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