Amphiphilic derivatives of (3β,17β)-3-hydroxyandrost-5-ene-17-carboxylic acid

• Published in: Steroids Vol. 128; pp. 58 - 67
• Main Authors: Özdemir, Zülal, Bildziukevich, Uladzimir, Šaman, David, Havlíček, Libor, Rárová, Lucie, Navrátilová, Lucie, Wimmer, Zdeněk
• Format: Journal Article
• Language: English
• Published: NEW YORK Elsevier Inc 01.12.2017; Elsevier
• Subjects: Amphiphile; Androstenes - chemical synthesis; Androstenes - chemistry; Androstenes - pharmacology; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial activity; Biochemistry & Molecular Biology; Carboxylic Acids - chemical synthesis; Carboxylic Acids - chemistry; Carboxylic Acids - pharmacology; Cytotoxicity; Diamine; Endocrinology & Metabolism; Escherichia coli - drug effects; Escherichia coli - pathogenicity; Life Sciences & Biomedicine; Microbial Sensitivity Tests; Polyamine; Polyamines - chemical synthesis; Polyamines - chemistry; Polyamines - pharmacology; Science & Technology; Steroid; Steroid; Diamine; Amphiphile; Cytotoxicity; Polyamine; Antimicrobial activity; CELLS; ANTIPROLIFERATIVE ACTIVITY; METABOLITES; SPERMINE; DEHYDROEPIANDROSTERONE; BREAST-CANCER; BETULINIC ACID; ESTERS; 2-METHOXYESTRADIOL; AROMATASE INHIBITORS
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2017.10.011

[Display omitted] •Amphiphilic derivatives of (3β,17β)-3-hydroxyandrost-5-ene-17-carboxylic acid studied.•Polyamine spermine and 1,2-diaminoethane, piperazine and cadaverine used as structural modifiers.•Facilitating cellular uptake and enhancing antitumor and antimicrobial properties.•Cytotoxicity of the target compounds on CEM found with selectivity.•Antimicrobial activity of the target compounds found. A series of amphiphilic derivatives of (3β,17β)-3-hydroxyandrost-5-ene-17-carboxylic acid (1) with the polyamine spermine and three other diamines, 1,2-diaminoethane, piperazine and cadaverine, were synthesized and their antimicrobial activity and cytotoxicity were investigated. Among the target compounds, several ones showed antimicrobial activity on Gram positive and Gram negative microorganisms. The most active compounds were 20 (Streptococcus mutans CCM 7409, 3.125 µM), 16 (Streptococcus mutans CCM 7409, 12.5 µM) and 10d (Escherichia coli CCM 3954, 12.5 µM). In addition, compounds 5d, 10d, 13 and 20 displayed cytotoxicity on CEM (12.1 ± 2.1 µM, 7.6 ± 1.0 µM, 19.0 ± 0.4 µM and 5.9 ± 0.7 µM, respectively). Two additional compounds displayed medium cytotoxicity on CEM, 5a (34.6 ± 5.2 µM) and 5c (37.7 ± 5.9 µM). The compound 13 and 20 displayed high toxicity also on normal fibroblasts.