Antimicrobial Activities of 3-Amino- and Polyaminosterol Analogues of Squalamine and Trodusquemine

Abstract

A series of 3-amino-and polyaminosterol analogues of squalamine and trodusquemine were synthesized and evaluated for their in vitro antimicrobial properties against human pathogens. The activity was highly dependent on the structure of the different compounds involved and the best results were obtained with aminosterol derivatives 4b, 4e, 8b, 8e and 8n exhibiting minimum inhibitory concentrations (MICs) against yeasts, Gram positive and Gram negative bacteria at average concentrations of 3.12 -12.5 mM.

Comparison of Proteomic Responses as Global Approach to Antibiotic Mechanism of Action Elucidation

“…As the study on trans-translation inhibitors shows, there is still much to learn about basic cellular processes. Salmi et al 62 and dissolved in 0.9% NaCl. Auranofin was purchased from Fisher Scientific, Hampton, USA.…”

Chemical Synthesis and Biological Effect on Xylem Formation of Xylemin and Its Analogues

“…[9] Subsequently, the Ns and Boc moieties were removed by Si-Thiol [10,11] and SOCl 2 /CH 3 OH, [9,12] respectively, to reach 18 and 19. We next examined the synthesis of N-(4aminobutyl)cyclohexylamine (22). When the alkylation conditions with bromocyclohexane (28)/Cs 2 CO 3 /TBAI, which were used for the synthesis of 6, 18, and 19, were applied to the synthesis of cyclohexylamine 30, the reaction did not proceed at all (Scheme 4a).…”

“…First, treatment of cyclohexylamine (31) with NsCl/NaHCO 3 [16] afforded the corresponding nitrobenzenesulfonamide, [17] which reacted with 4bromobutyronitrile (32) in the presence of Cs 2 CO 3 and TBAI [9] to provide the alkylated product 33 (Scheme 5a). Deprotection of the nitrobenzenesulfonamide 33 with Si-Thiol [10,11] and subsequent hydrogenation of the nitrile group with PtO 2 [17] were performed to produce the desired N-(4aminobutyl)cyclohexylamine (22). [13] Furthermore, the synthetic sequence from 31 to 22 was successfully applied to amines 34, 36, and 38 to deliver the designed N-(4-aminobutyl)alkylamines 21, [17] 23, and 20 (Scheme 5b-d).…”

“…[20] These reaction conditions were successfully applied to the synthesis of various secondary amines by Brunel and co-workers in 2006. [21] When these reaction conditions were used in our cases, thus, reaction of 40 with 2 (3.0 equiv) in the presence of Ti(OiPr) 4 in CH 3 OH at room temperature and subsequent reduction with NaBH 4 at -78 °C took place, [22] the desired product 22 was produced in 68% yield (Entry 3). Changing the reaction temperature from -78 °C to 0 °C in reduction step increased the chemical yield of 22 to 84% yield (Entry 4).…”

An İnnovative Molecule To Combat İnfectious Agents: Squalamine

“…Salmi ve ark. (31) yaptıkları bir çalışmada, aminosterollerin antifungal etkisini sınırlı sayıdaki maya suşunda bildirmişlerdir. 2011 yılında yapılan başka bir çalışmada ise, araştırıcılar fungemi vakalarından topladıkları 21 maya izolatına karşı skualamin'in hücre içi ATP atılımını indükleyerek mayaların hücre membranında bozulmaya yol açtığını ve bu şekilde fungisid etki gösterdiğini saptamışlardır (28) .…”