3235-69-6Relevant articles and documents
Design, synthesis and biological evaluation of HIV-1 protease inhibitors with morpholine derivatives as P2 ligands in combination with cyclopropyl as P1′ ligand
Dong, Biao,Dou, Yue,Wang, Ju-Xian,Wang, Yu-Cheng,Zhang, Fan,Zhang, Guo-Ning,Zhu, Mei
, (2020)
A series of novel HIV-1 protease inhibitors has been designed and synthesized, which contained morpholine derivatives as the P2 ligands and hydrophobic cyclopropyl as the P1′ ligand at the meantime in this study, with the aim of improving the interactions between the active sites of HIV-1 protease and the inhibitors. Twenty-eight compounds were synthesized and assessed, among which inhibitors m18 and m1 exhibited excellent inhibitory effect on the activity of HIV-1 protease with IC50 value of 47 nM and 53 nM, respectively. The molecular modeling of m1 revealed possible hydrogen bondings or van der Waals between the inhibitor and the protease, worthy of in-depth study.
Nitrogen-containing cyclic compounds as iminium ion sources for selected reaction monitoring detection of derivatized analytes
?ilionis, Andrius
supporting information, p. 25 - 35 (2019/09/03)
Liquid chromatography–tandem mass spectrometry is one of the most sensitive tools for determination of trace amounts of analytes in metabolomics and proteomics. The highest sensitivity is achieved in selected reaction monitoring detection, which involves fragmentation of the molecular ion between two levels of mass selection. However, fragmentation of some compounds is complicated. Detection sensitivity of such analytes may be increased by derivatizing them with a specific moiety fragmentation of which results in product ion of high abundance. In this work, we reveal the influence of iminium ions' structures on their stability by comparing six nitrogen-containing cyclic compounds as derivatization reagents for tandem mass spectrometric analysis of amino group-containing analyte. Commercially available starting materials (piperidine, 2,6-dimethylpiperidine, 1-methylpiperazine, morpholine, pyrrolidine and 1-cyanomethyl-3-methylimidazolium ionic liquid) were used for the synthesis of corresponding carboxylic acids which were further used for derivatization of the model analyte tryptamine. Liquid chromatographic–mass spectrometric analysis of differently derivatized tryptamine was performed for the evaluation of release and stability of corresponding iminium ions under collision-induced dissociation conditions. As a result, morpholine moiety was shown being the most promising iminium ion source among tested compounds. Possible sub-fragmentation pathways of investigated iminium ions were discussed, and the structures of secondary product ions were proposed.
Development of a series of bis-triazoles as G-quadruplex ligands
Saleh, Maysaa M.,Laughton, Charles A.,Bradshaw, Tracey D.,Moody, Christopher J.
, p. 47297 - 47308 (2017/10/19)
Maintenance of telomeres-specialized complexes that protect the ends of chromosomes-is provided by the enzyme complex telomerase, which is a key factor that is activated in more than 80% of cancer cells, but absent in most normal cells. Targeting telomere maintenance mechanisms could potentially halt tumour growth across a broad spectrum of cancer types. Telomeric ends of chromosomes consist of noncoding repeat sequences of guanine-rich DNA. These G-rich ends can fold into structures called G-quadruplexes. Stabilization of G-quadruplexes by small binding molecules called G4 ligands can prevent telomerase enzyme from maintaining telomere integrity in cancer cells. G-quadruplexes can exist in other parts of the genome too, especially within promoter sequences of oncogenes, and also be interesting drug targets. Here, we describe the development of a new series of novel bis-triazoles, designed to stabilize G-quadruplex structures selectively as G4 ligands. FRET assays showed two compounds to be moderately effective G4 binders, with particular affinity for the quadruplex formed by the Hsp90a promoter sequence, and good selectivity for G-quadruplex DNA vs. duplex DNA. However, CD spectroscopy failed to provide any information about the folding topology of the human telomeric G-quadruplex resulting from its interaction with one of the ligands. All the new ligands showed potent cell growth inhibitory properties against human colon and pancreatic cancer cell lines, as evidenced by the MTT assay; notably, they were more potent against cancer cells than in fetal lung fibroblasts. Docking studies were performed to rationalize the affinity of these ligands for binding to the telomeric parallel G-quadruplex DNA.
