Synthesis and biological evaluation of a new series of N-acyldiamines as potential antibacterial and antifungal agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 24; no. 19; pp. 4626 - 4629
• Main Authors: Ferreira, Bianca da S., de Almeida, Angelina M., Nascimento, Thiago C., de Castro, Pedro P., Silva, Vania L., Diniz, Claúdio G., Le Hyaric, Mireille
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.10.2014; Elsevier
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial; Antifungal; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Candida - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Diamines - chemical synthesis; Diamines - chemistry; Diamines - pharmacology; Dose-Response Relationship, Drug; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Life Sciences & Biomedicine; Lipophilicity; Microbial Sensitivity Tests; Molecular Structure; MRSA; N-Acyldiamines; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Structure-Activity Relationship; N-Acyldiamines; Antifungal; Antibacterial; Lipophilicity; MRSA; FATTY-ACIDS; DERIVATIVES; ANTIMICROBIAL ACTIVITY
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2014.08.047

In continuation of our efforts to find new antimicrobial compounds, series of fatty N-acyldiamines were prepared from fatty methyl esters and 1,2-ethylenediamine, 1,3-propanediamine or 1,4-butanediamine. The synthesized compounds were screened for their antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis), Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and for their antifungal activity against four species of Candida (C. albicans, C. tropicalis, C. glabrata and C. parapsilosis). Compounds 5a (N-(2-aminoethyl)dodecanamide), 5b (N-(2-aminoethyl)tetracanamide) and 6d (N-(3-aminopropyl)oleamide) were the most active against Gram-positive bacteria, with MIC values ranging from 1 to 16μg/mL and were evaluated for their activity against 21 clinical isolates of methicillin-resistant S. aureus. All the compounds exhibited good to moderate antifungal activity. Compared to chloramphenicol, compound 6b displayed a similar activity (MIC50=16μg/mL). A positive correlation could be established between lipophilicity and biological activity.