New Triazacycloalkane Derivatives as Cytotoxic Agents for CLL Treatment: From Proof of Concept to the Targeting Biomolecule was written by Marlin, Axia;Le Pape, Fiona;Le Goff, Jocelyn;Hamon, Nadege;Troadec, Thibault;Tripier, Raphael;Berthou, Christian;Patinec, Veronique. And the article was included in Bioconjugate Chemistry in 2022.Safety of (4-Bromopyridin-2-yl)methanol This article mentions the following:
The 1,4,7-tris-(2-pyridinylmethyl)-1,4,7-triazacyclononane ligand (no3py) and its bifunctional analog no3pyCOOK were synthesized to investigate their action toward zinc(II) depletion related to the apoptosis phenomenon in chronic lymphocytic leukemia (CLL) cells. no3py was used as the “free” ligand, while its “graftable” derivative was conjugated on a newly synthesized bifunctional sialoglycan, 6′-SL-NH2, selected to specifically bind CD22 biomarker expressed on the B-CLL cell surface. Both compounds were produced with good yields thanks to a Sonogashira coupling reaction and an orthoester function, resp., for the chelator and the targeting moiety. The newly reported bioconjugate 6′-SL-no3py was then obtained through a peptidic coupling reaction. Biol. in vitro studies of no3py and 6′-SL-no3py consisting of real-time detection of cell health (cytotoxicity and proliferation) and caspases 3/7 activation (crucial enzymes whose activation triggers cell death signaling pathways) have been investigated. First, Ramos, Daudi, and Raji B-cell lines, which present different sensitivity to zinc(II) content variation, were incubated with no3py and 6′-SL-no3py. Then, a videomicroscope allowed the real-time monitoring of the morphol. changes leading to cell death from the detection of the cytotoxicity, the antiproliferative effect, and the caspasic activity. In terms of mechanism, the Zn2+ chelator cytotoxic effect of no3py has been evidenced by a culture medium ion supplementation study and by the decrease of intracellular fluorescence of Zn-specific fluorophore zinquin in the presence of no3py and 6′-SL-no3py chelators. Finally, flow cytometry anal. with classical Annexin V staining was conducted to detect no3py- and 6′-SL-no3py-induced apoptotic cell death in B-CLL cells. Time-course anal., using the Incucyte Live-Cell Anal. System, demonstrated that no3py induced cell death in a time- and dose-dependent manner with variability across cell lines. 6′-SL-no3py exhibited the same dose-dependent trend as no3py, showing the efficiency of the targeting moiety. In both cases, the chelators depicted proliferation curves that were inversely correlated with kinetic death. Morphol. changes specific to apoptosis and caspase 3/7 activation were observed for the three cell lines treated with no3py and 6′-SL-no3py, highlighting their role as apoptotic agents. A higher concentration of 6′-SL-no3py is needed to reach 50% of the B-CLL mortality, confirming a targeting of the chelator to the cell membrane. Overall, our results proved that the biol. properties of the triazamacrocyclic chelator still remain even after addition of the targeting moiety. The free chelator as well as the bioconjugate constitute promising cytotoxic agents for CLL therapy through apoptosis induction. In the experiment, the researchers used many compounds, for example, (4-Bromopyridin-2-yl)methanol (cas: 131747-45-0Safety of (4-Bromopyridin-2-yl)methanol).
(4-Bromopyridin-2-yl)methanol (cas: 131747-45-0) belongs to pyridine derivatives. Pyridines are an important class of heterocycles and occur in polysubstituted forms in many naturally occurring biologically active compounds, drug molecules and chiral ligands. Reduced pyridines, namely tetrahydropyridines, dihydropyridines and piperidines, are found in numerous natural and synthetic compounds. The synthesis and reactivity of these compounds have often been driven by the fact many of these compounds have interesting and unique pharmacological properties. Safety of (4-Bromopyridin-2-yl)methanol