Amide derivatives of partricin A with potent antifungal activity

• Published in: European journal of medicinal chemistry Vol. 31; no. 12; pp. 965 - 972
• Main Authors: Bruzzese, T, Rimaroli, C, Bonabello, A, Ferrari, E, Signorini, M
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Masson SAS 1996; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; antifungal activity; Biological and medical sciences; Medical sciences; Miscellaneous. Antibiotics with multiple activities; partricin A amide; Pharmacology. Drug treatments; polyene antibiotic; structure-activity relationship; polyene antibiotic; partricin A amide; antifungal activity; structure-activity relationship; Conjugated polyenic compound; Toxicity; Acute; Rodentia; Lactone; Oxygen heterocycle; In vitro; Macrolide; Macrocycle; Antiprotozoal agent; In vivo; Vertebrata; Antibiotic; Antifungal agent; Mammalia; Structure activity relation; Mouse; Aminoglycoside; Animal; Parasiticid; Bicyclic compound; Carboxamide; Chemical synthesis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/S0223-5234(97)86175-2

A series of partricin A amides were synthesized using the active ester method by reaction with several amines on the carboxy group and then with some acids on the mycosamine group of partricin A. Most of the derivatives are more potent antifungals than the known reference standards, including amphotericin B, and a few are also less toxic and less hemolytic. Amides substituted with basic groups may give hydrosoluble salts, useful for injectable formulations, and two derivatives were selected for further development, namely, partricin A 2-dimethylaminoethyl amide (
10, SPA-S-710) and
N-dimethylaminoacetyl-partricin A 2-dimethylaminoethyl amide (
22, SPA-S-752).