1202779-52-9Relevant academic research and scientific papers
Anticancer activity of small amphipathic β2,2-amino acid derivatives
Hansen, Terkel,Ausbacher, Dominik,Zachariassen, Zack G.,Anderssen, Trude,Havelkova, Martina,Strom, Morten B.
, p. 22 - 29 (2013/02/23)
We report the anticancer activity from screening of a series of synthetic β2,2-amino acid derivatives that were prepared to confirm the pharmacophore model of short cationic antimicrobial peptides with high anti-Staphylococcal activity. The most potent derivatives against human Burkitt's lymphoma (Ramos) cells displayed IC50 values below 8 μM, and low toxicity against human red blood cells (EC50 > 200 μM). A more than 5-fold preference for Ramos cancer cells compared to human lung fibroblasts (MRC-5 cells) was also obtained for the most promising β2,2-amino acid derivative 3-amino-N-(2-aminoethyl)-2,2- bis(naphthalen-2-ylmethyl)propanamide (5c). Screening of 5c at the National Cancer Institute (NCI, USA) confirmed its anticancer potency and revealed a very broad range of anticancer activity with IC50 values of 0.32-3.89 μM against 59 different cancer cell lines. Highest potency was obtained against the colon cancer cell lines, a non-small cell lung cancer, a melanoma, and three leukemia cell lines included in the NCI screening panel. The reported β2,2-amino acid derivatives constitute a promising new class of anticancer agents based on their high anticancer potency, ease of synthesis, mode-of-action, and optimized pharmacokinetic properties compared to much larger antimicrobial peptides.
Antimicrobial activity of small β-peptidomimetics based on the pharmacophore model of short cationic antimicrobial peptides
Hansen, Terkel,Alst, Tore,Havelkova, Martina,Str?m, Morten B.
experimental part, p. 595 - 606 (2010/06/19)
We have synthesized a series of small β-peptidomimetics (Mw 2,2-amino acid coupled to a C-terminal L-arginine amide residue. By varying the lipophilic side-chains of the β2,2-amino acids, we obtained a series of highly potent β-peptidomimetics with high enzymatic stability against α-chymotrypsin and a general low toxicity against human erythrocytes. The most potent β-peptidomimetics displayed minimal inhibitory concentrations of 2.1-7.2 μM against Staphylococcus aureus, methicillin resistant Staphylococcus aureus (MRSA), methicillin resistant Staphylococcus epidermidis (MRSE), and Escherichia coli. Small amphipathic β-peptidomimetics may be a promising class of antimicrobial agents by means of having a similar range of potency and selectivity as larger cationic antimicrobial peptides in addition to improved enzymatic stability and lower costs of production.
