Synthesis and antimicrobial activity of novel amphiphilic aromatic amino alcohols

• Published in: Bioorganic & medicinal chemistry letters Vol. 23; no. 10; pp. 2883 - 2887
• Main Authors: de Almeida, Angelina M., Nascimento, Thiago, Ferreira, Bianca S., de Castro, Pedro P., Silva, Vânia L., Diniz, Claúdio G., Le Hyaric, Mireille
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.05.2013; Elsevier
• Subjects: 2-Amino-2-hydroxymethyl-propane-1,3-diol; Alkyloxybenzaldehyde; Amino alcohol; amino alcohols; Amino Alcohols - chemical synthesis; Amino Alcohols - chemistry; Amino Alcohols - pharmacology; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antibacterial properties; antibiotics; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; antifungal properties; Antimicrobial activity; Bacteria - drug effects; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Dose-Response Relationship, Drug; Escherichia coli; Fungi - drug effects; Gram-positive bacteria; hydrophobicity; Life Sciences & Biomedicine; Molecular Structure; MRSA; Pharmacology & Pharmacy; Physical Sciences; Pseudomonas aeruginosa; Reductive amination; Science & Technology; Staphylococcus aureus; Staphylococcus epidermidis; Structure-Activity Relationship; Surface-Active Agents - chemical synthesis; Surface-Active Agents - chemistry; Surface-Active Agents - pharmacology; yeasts; Reductive amination; Amino alcohol; Antimicrobial activity; Alkyloxybenzaldehyde; MRSA; 2-Amino-2-hydroxymethyl-propane-1,3-diol
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.03.078

We report in this work the preparation and in vitro antimicrobial evaluation of novel amphiphilic aromatic amino alcohols synthesized by reductive amination of 4-alkyloxybenzaldehyde with 2-amino-2-hydroxymethyl-propane-1,3-diol. The antibacterial activity was determined against four standard strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa) and 21 clinical isolates of methicillin-resistant Staphylococcus aureus. The antifungal activity was evaluated against four yeast (Candida albicans, Candida tropicalis, Candida glabrata and Candida parapsilosis). The results obtained showed a strong positive correlation between the lipophilicity and the antibiotic activity of the tested compounds. The best activities were obtained against the Gram-positive bacteria (MIC=2–16μgml−1) for the five compounds bearing longer alkyl chains (4c–g; 8–14 carbons), which were also the most active against Candida (MIC=2–64μgml−1). Compound 4e exhibited the highest levels of inhibitory activity (MIC=2–16μgml−1) against clinical isolates of MRSA. A concentration of twice the MIC resulted in bactericidal activity of 4d against 19 of the 21 clinical isolates.