51513-80-5Relevant articles and documents
Design and evaluation of analogues of the bacterial cell-wall peptidoglycan motif l-Lys-d-Ala-d-Ala for use in a vancomycin biosensor
Hernout, Olivier,Berthoin, Karine,Delattre, Isabelle,Tulkens, Paul M.,Carryn, Stephane,Marchand-Brynaert, Jacqueline
, p. 5758 - 5762 (2007)
Four small molecular receptors of vancomycin have been designed to make part of a novel biosensor device based on the FTIR-ATR detection: N-Boc (2a) or N-Ac (2b)-6-aminocaproyl-d-Ala-d-Ala and N-Boc (3a) or N-Ac (3b)-6-aminocaproyl-d-Ala-d-Ser. Using an original microbiological approach to assess the competition of compounds with the natural target of vancomycin in bacteria, EC50 values of 6.3-8.0 × 10-5 M (2a-b) and 7.1-9.3 × 10-4 M (3a-b) were determined. Vancomycin:2b complex was characterized by MS.
Molecular Umbrellas Modulate the Selective Toxicity of Polyene Macrolide Antifungals
Skwarecki, Andrzej S.,Skarbek, Kornelia,Martynow, Dorota,Serocki, Marcin,Bylińska, Irena,Milewska, Maria J.,Milewski, S?awomir
, p. 1454 - 1465 (2018/04/23)
Antifungal polyene macrolide antibiotics Amphotericin B (AmB) and Nystatin (NYS) were conjugated through the ω-amino acid linkers with diwalled "molecular umbrellas" composed of spermidine-linked deoxycholic or cholic acids. The presence of "umbrella" substituents modulated biological properties of the antibiotics, especially their selective toxicity. Some of the AmB-umbrella conjugates demonstrated antifungal in vitro activity comparable to that of the mother antibiotic but diminished mammalian toxicity, especially the hemolytic activity. In contrast, antifungal in vitro activity of NYS-umbrella conjugates was strongly reduced and all these conjugates demonstrated poorer than NYS selective toxicity. No correlation between the aggregation state and hemolytic activity of the novel conjugates was found.
Quinone-amino acid conjugates targeting leishmania amino acid transporters
Prati, Federica,Goldman-Pinkovich, Adele,Lizzi, Federica,Belluti, Federica,Koren, Roni,Zilberstein, Dan,Bolognesi, Maria Laura
, (2015/01/08)
The aim of the present study was to investigate the feasibility of targeting Leishmania transporters via appropriately designed chemical probes. Leishmania donovani, the parasite that causes visceral leishmaniasis, is auxotrophic for arginine and lysine and has specific transporters (LdAAP3 and LdAAP7) to import these nutrients. Probes 1-15 were originated by conjugating cytotoxic quinone fragments (II and III) with amino acids (i.e. arginine and lysine) by means of an amide linkage. The toxicity of the synthesized conjugates against Leishmania extracellular (promastigotes) and intracellular (amastigotes) forms was investigated, as well their inhibition of the relevant amino acid transporters. We observed that some conjugates indeed displayed toxicity against the parasites; in particular, 7 was identified as the most potent derivative (at concentrations of 1 μg/mL and 2.5 μg/mL residual cell viability was reduced to 15% and 48% in promastigotes and amastigotes, respectively). Notably, 6, while retaining the cytotoxic activity of quinone II, displayed no toxicity against mammalian THP1 cells. Transport assays indicated that the novel conjugates inhibited transport activity of lysine, arginine and proline transporters. Furthermore, our analyses suggested that the toxic conjugates might be translocated by the transporters into the cells. The non-toxic probes that inhibited transport competed with the natural substrates for binding to the transporters without being translocated. Thus, it is likely that 6, by exploiting amino acid transporters, can selectively deliver its toxic effects to Leishmania cells. This work provides the first evidence that amino acid transporters of the human pathogen Leishmania might be modulated by small molecules, and warrants their further investigation from drug discovery and chemical biology perspectives.
