69754-49-0Relevant academic research and scientific papers
Design, synthesis and structure-activity relationship studies of novel sirtuin 2 (SIRT2) inhibitors with a benzamide skeleton
Sakai, Taki,Matsumoto, Yotaro,Ishikawa, Minoru,Sugita, Kazuyuki,Hashimoto, Yuichi,Wakai, Nobuhiko,Kitao, Akio,Morishita, Era,Toyoshima, Chikashi,Hayashi, Tomoatsu,Akiyama, Tetsu
, p. 328 - 339 (2015)
Human sirtuin 2 (SIRT2) is an attractive target molecule for development of drugs to treat neurodegenerative diseases and cancer, because SIRT2 inhibitors have a protective effect against neurodegeneration and an anti-proliferative effect on cancer stem c
Discovery of a Novel Mycobacterial F-ATP Synthase Inhibitor and its Potency in Combination with Diarylquinolines
Anbarasu, Sivaraj,Bates, Roderick W.,Dick, Thomas,Dr?ge, Peter,Grüber, Gerhard,Harikishore, Amaravadhi,Hotra, Adam,Kalia, Nitin Pal,Kalyanasundaram, Revathy,Lakshmanan, Umayal,Makhija, Harshyaa,Ng, Pearly Shuyi,Parthasarathy, Krupakar,Pethe, Kevin,Poulsen, Anders,Pradeep, Chaudhari Namrata,Ragunathan, Priya,Sae-Lao, Patcharaporn,Sarathy, Jickky Palmae,Saw, Wuan-Geok,Seankongsuk, Pattarakiat,Shin, Joon,Tan, Jocelyn Hui Ling
, p. 13295 - 13304 (2020/06/03)
The F1FO-ATP synthase is required for growth and viability of Mycobacterium tuberculosis and is a validated clinical target. A mycobacterium-specific loop of the enzyme's rotary γ subunit plays a role in the coupling of ATP synthesis within the enzyme complex. We report the discovery of a novel antimycobacterial, termed GaMF1, that targets this γ subunit loop. Biochemical and NMR studies show that GaMF1 inhibits ATP synthase activity by binding to the loop. GaMF1 is bactericidal and is active against multidrug- as well as bedaquiline-resistant strains. Chemistry efforts on the scaffold revealed a dynamic structure activity relationship and delivered analogues with nanomolar potencies. Combining GaMF1 with bedaquiline or novel diarylquinoline analogues showed potentiation without inducing genotoxicity or phenotypic changes in a human embryonic stem cell reporter assay. These results suggest that GaMF1 presents an attractive lead for the discovery of a novel class of anti-tuberculosis F-ATP synthase inhibitors.
N-Phenylbenzamide derivatives as alternative oxidase inhibitors: Synthesis, molecular properties, 1H-STD NMR, and QSAR
Barsottini, Mario R. O.,Carazzolle, Marcelo F.,Costa, Paulo C. S.,Evangelista, Joel S.,Miranda, Paulo C. M. L.,Nascimento, Andrey F. Z.,Pereira, Gon?alo A. G.,Pires, Bárbara A.,Rocco, Silvana A.,Sfor?a, Maurício L.,Silva, Jaqueline S.,Vieira, Maria L. L.,Zeri, Ana C. M.
, (2020/02/27)
In the present work, 117 N-phenylbenzamides (NPDs) were prepared and evaluated against recombinant AOX from the fungal pathogen Moniliophthora perniciosa. 1H, 13C NMR, FTIR, and mass spectra provided structural information on NPDs. The library compounds were tested as Alternative Oxidase inhibitors in two different assays using the model yeast Pichia pastoris: cell growth and oxygen consumption assays. The most active compound, 3FH, was further characterized by DRX and 1H-NMR-STD. Single crystal X-ray diffraction showed intra- and intermolecular interactions of 3FH in solid-state and elucidated its 3D structural configuration. 1H-NMR-STD allowed us to derive protein-ligand interactions in a membrane-mimetic system and evidenced an outstanding interaction of 3FH with this enzyme. Results of both biological assays were used as input to Quantitative Structure-Activity Relationship models, which highlighted the more important molecular fragments contributions for protein-ligand interaction.
