71083-06-2Relevant articles and documents
3-(Benzo[: D] thiazol-2-yl)-4-aminoquinoline derivatives as novel scaffold topoisomerase i inhibitor via DNA intercalation: Design, synthesis, and antitumor activities
Chen, Nan-Ying,Gu, Zi-Yu,Li, Xiao-Juan,Liao, Hao-Ran,Mo, Dong-Liang,Pan, Cheng-Xue,Su, Gui-Fa,Yuan, Jing-Mei,Zhang, Guo-Hai
, p. 11203 - 11214 (2020/07/15)
Twenty-seven 3-(benzo[d]thiazol-2-yl)-4-aminoquinoline derivatives have been designed and synthesized as topoisomerase I inhibitors. The in vitro anti-proliferation evaluation against four human cancer cell lines (MGC-803, HepG-2, T24, and NCI-H460) and one normal cell line (HL-7702) indicated that most of them exhibited potent cytotoxicity. Among them, 5a was identified as the most promising candidate with a low IC50 value of about 2.20 ± 0.14 and was selected for further exploration. Spectroscopic analyses and agarose-gel electrophoresis assays indicated that 5a could interact with DNA and strongly inhibit topoisomerase I (Topo I). Further screening of the Topo I activity of compounds 5b, 5c, 5e, 5f, 5h, 5i, 5j, 5l, and 5n suggested that some of the compounds might exert quite a different cytotoxicity profile to that of 5a. Molecular modeling studies confirmed that 5a adopts a unique mode to interact with DNA and Topo I. Other molecular mechanistic studies suggested that the treatment of MGC-803 cells with 5a induces S phase arrest, up-regulates the pro-apoptotic protein, down-regulates the anti-apoptotic protein, activates caspase-3, and subsequently induces mitochondrial dysfunction so as to induce cell apoptosis. The in vivo efficiency of 5a was also evaluated on MGC-803 xenograft nude mice and the relative tumor growth inhibition was 42.4percent at 12 mg kg-1 without an obvious loss in the body weight. This journal is
A Photoswitchable Dualsteric Ligand Controlling Receptor Efficacy
Agnetta, Luca,Kauk, Michael,Canizal, Maria Consuelo Alonso,Messerer, Regina,Holzgrabe, Ulrike,Hoffmann, Carsten,Decker, Michael
supporting information, p. 7282 - 7287 (2017/06/13)
The investigation of the mode and time course of the activation of G-protein-coupled receptors (GPCRs), in particular muscarinic acetylcholine (mACh or M) receptors, is still in its infancy despite the tremendous therapeutic relevance of M receptors and GPCRs in general. We herein made use of a dualsteric ligand that can concomitantly interact with the orthosteric, that is, the neurotransmitter, binding site and an allosteric one. We synthetically incorporated a photoswitchable (photochromic) azobenzene moiety. We characterized the photophysical properties of this ligand called BQCAAI and investigated its applicability as a pharmacological tool compound with a set of FRET techniques at the M1 receptor. BQCAAI proved to be an unprecedented molecular tool; it is the first photoswitchable dualsteric ligand, and its activity can be regulated by light. We also applied BQCCAI to investigate the time course of several receptor activation processes.
Regiocontrolled Nitration of 4-Quinolones at Ambient Conditions
Sarkar, Sonali,Ghosh, Prasanjit,Misra, Anirban,Das, Sajal
, p. 2386 - 2393 (2015/10/12)
Regiocontrolled nitration of 4-quinolone, the highly privileged scaffold, has been developed at ambient conditions. The nitro group can selectively be introduced at diverse positions simply by tuning the reactivity of the moiety. Discrimination is being achieved through the selective functionalization of the free N-H group. The functional group has been screened theoretically with the help of Fukui function and local softness calculation. Theoretical predictions are synchronized well with the experimental findings. Finally, this nitration technique allows quick access to the structurally diverse 4-quinolones.
