66444-27-7Relevant academic research and scientific papers
Antinociceptive and cytotoxic activity of opioid peptides with hydrazone and hydrazide moieties at the C-terminus
Bochynska-Czyz, Marta,Dyniewicz, Jolanta,Kosson, Piotr,Lipinski, Piotr F. J.,Matalinska, Joanna,Misicka, Aleksandra
, (2020)
In the present contribution, we analyze the influence that C-terminal extension of short opioid peptide sequences by organic fragments has on receptor affinity, in vivo analgesic activity, and antimelanoma properties. The considered fragments were based on either N-acylhydrazone (NAH) or N0-acylhydrazide motifs combined with the 3,5-bis(trifluoromethyl)phenyl moiety. Eleven novel compounds were synthesized and subject to biological evaluation. The analyzed compounds exhibit a diversified range of affinities for the μ opioid receptor (MOR), rather low δ opioid receptor (DOR) affinities, and no appreciable neurokinin-1 receptor binding. In three out of four pairs, N-acylhydrazone-based derivatives bind MOR better than their N’-acylhydrazide counterparts. The best of the novel derivatives have similar low nanomolar MOR binding affinity as the reference opioids, such as morphine and biphalin. The obtained order of MOR affinities was compared to the results of molecular docking. In vivo, four tested compounds turned out to be relatively strong analgesics. Finally, the NAH-based analogues reduce the number of melanoma cells in cell culture, while their N0-acylhydrazide counterparts do not. The antimelanoma properties are roughly correlated to the lipophilicity of the compounds.
Biological activity of fragments and analogues of the potent dimeric opioid peptide, biphalin
Lipkowski, Andrzej W.,Misicka, Aleksandra,Davis, Peg,Stropova, Dagmar,Janders, Jacqueline,Lachwa, Magdalena,Porreca, Frank,Yamamura, Henry I.,Hruby, Victor J.
, p. 2763 - 2766 (1999)
The synthesis and biological activity of two fragments of the very potent opioid peptide biphalin, showed that Tyr-D-Ala-Gly-Phe-NH-NH-Phe is the minimal fragment necessary to express equal affinities and the same biological activity profile as the paren
Hydrazone linker as a useful tool for preparing chimeric peptide/ Nonpeptide bifunctional compounds
Dyniewicz, Jolanta,Lipinski, Piotr F. J.,Kosson, Piotr,Lesniak, Anna,Bochynska-Czyz, Marta,Muchowska, Adriana,Tourwe, Dirk,Ballet, Steven,Misicka, Aleksandra,Lipkowski, Andrzej W.
, p. 73 - 77 (2017/12/12)
The area of multitarget compounds, joining two pharmacophores within one molecule, is a vivid field of research in medicinal chemistry. Not only pharmacophoric elements are essential for the design and activity of such compounds, but the type and length o
Development of novel enkephalin analogues that have enhanced opioid activities at both μ and δ opioid receptors
Yeon, Sun Lee,Petrov, Ravil,Park, Chad K.,Ma, Shou-Wu,Davis, Peg,Lai, Josephine,Porreca, Frank,Vardanyan, Ruben,Hruby, Victor J.
, p. 5528 - 5532 (2008/03/13)
Enkephalin analogues with a 4-anilidopiperidine scaffold have been designed and synthesized to achieve therapeutic benefit for the treatment of pain due to mixed μ and δ opioid agonist activities. Ligand 16, in which a Dmt-substituted enkephalin-like stru
