29182-94-3Relevant academic research and scientific papers
Synthesis and Antifungal Activity of New N-Aryl-2-(2-hydroxyphenylamino)ethylenediamine Derivatives
Gao, Han,Wan, Yichao,Tan, Yuhuan,Luo, Xi,Li, Lin
, p. 122 - 127 (2021/02/21)
Abstract: In this study, a series of new N-aryl-2-(2-hydroxyphenylamino)ethylenediamine derivatives has beendesigned, synthesized and evaluated for antifungal activity against six selectedspecies of phytopathogenic fungi. Among the products, the most potent compoundhave demonstrated 97.7% inhibitory activity against S.sclerotiorum at the concentration of 50 μg/mL, which is higherthan that of the positive control chlorothalonil.
Structure–activity relationship and biological evaluation of 12 N-substituted aloperine derivatives as PD-L1 down-regulatory agents through proteasome pathway
Zeng, Qing–Xuan,Wang, Kun,Zhang, Xin,Shi, Yu-Long,Dou, Yue–Ying,Guo, Zhi–Hao,Zhang, Xin–Tong,Zhang, Na,Deng, Hong–Bin,Li, Ying–Hong,Song, Dan–Qing
, (2021/10/22)
Twenty-nine 12 N-substituted aloperine derivatives were synthesized and screened for suppression on PD-L1 expression in H460 cells, as a continuation of our work. Systematic structural modifications led to the identification of compound 6b as the most act
Design, synthesis, fungicidal activity and molecular docking studies of novel 2-((2-hydroxyphenyl)methylamino)acetamide derivatives
Tang, Zilong,Li, Xinxing,Yao, Yuan,Qi, Yongcun,Wang, Ming,Dai, Ningning,Wen, Yuhao,Wan, Yichao,Peng, Lifen
, p. 2572 - 2578 (2019/03/26)
A series of novel 2-hydroxyphenyl substituted aminoacetamides was designed by molecular hybridization of the aminoacetamide scaffold and 2-hydroxyphenyl motif. The target compounds were synthesized and their fungicidal activities were evaluated. Some of the target compounds showed excellent antifungal activities against S. sclerotiorum and P. capsici. Significantly, compounds 5e displayed the most potent activity against S. sclerotiorum with EC50 = 2.89 μg/mL, which was lower than that of commercial chlorothalonil. The systematic studies provided strong confidence that the hydroxyl group and the carbonyl group are crucial for the fungicidal activity. Molecular docking studies suggest that SDH enzyme could be one of the potential action targets of our compounds.
Synthesis and cytotoxicity of thieno[2,3-b]quinoline-2-carboxamide and cycloalkyl[b]thieno[3,2-e]pyridine-2-carboxamide derivatives
Leung, Euphemia,Pilkington, Lisa I.,van Rensburg, Michelle,Jeon, Chae Yeon,Song, Mirae,Arabshahi, Homayon J.,De Zoysa, Gayan Heruka,Sarojini, Vijayalekshmi,Denny, William A.,Reynisson, Jóhannes,Barker, David
supporting information, p. 1142 - 1154 (2019/05/24)
Seventy nine derivatives of thieno[2,3-b]quinolines, tetrahydrothieno[2,3-b]quinoline, dihydrocyclopenta[b]thieno[3,2-e]pyridine, cyclohepta[b]thieno[3,2-e]pyridine and hexahydrocycloocta[b]thieno[3,2-e]pyridine were either synthesized or obtained commercially and tested for their antiproliferative activity against HCT116, MDA-MB-468 and MDA-MB-231 human cancer cell lines. The most potent eight compounds were active against all cell lines with IC50 values in the 80–250 nM range. In general hexahydrocycloocta[b]thieno[3,2-e]pyridines were most active with increasing activity observed as larger cycloalkyl rings were fused to the pyridine ring.
Searching for New Leads for Tuberculosis: Design, Synthesis, and Biological Evaluation of Novel 2-Quinolin-4-yloxyacetamides
Pitta, Eleni,Rogacki, Maciej K.,Balabon, Olga,Huss, Sophie,Cunningham, Fraser,Lopez-Roman, Eva Maria,Joossens, Jurgen,Augustyns, Koen,Ballell, Lluis,Bates, Robert H.,Van Der Veken, Pieter
supporting information, p. 6709 - 6728 (2016/08/05)
In this study, a new series of more than 60 quinoline derivatives has been synthesized and evaluated against Mycobacterium tuberculosis (H37Rv). Apart from the SAR exploration around the initial hits, the optimization process focused on the improvement of the physicochemical properties, cytotoxicity, and metabolic stability of the series. The best compounds obtained exhibited MIC values in the low micromolar range, excellent intracellular antimycobacterial activity, and an improved physicochemical profile without cytotoxic effects. Further investigation revealed that the amide bond was the source for the poor blood stability observed, while some of the compounds exhibited hERG affinity. Compound 83 which contains a benzoxazole ring instead of the amide group was found to be a good alternative, with good blood stability and no hERG affinity, providing new opportunities for the series. Overall, the obtained results suggest that further optimization of solubility and microsomal stability of the series could provide a strong lead for a new anti-TB drug development program.
SAR and identification of 2-(quinolin-4-yloxy)acetamides as Mycobacterium tuberculosis cytochrome bc 1 inhibitors
Phummarin, Narisa,Boshoff, Helena I.,Tsang, Patricia S.,Dalton, James,Wiles, Siouxsie,Barry, Clifton E.,Copp, Brent R.
, p. 2122 - 2127 (2016/11/18)
A previous phenotypic screen by GSK identified 2-(quinolin-4-yloxy)acetamides as potent growth inhibitors of Mycobacterium tuberculosis (Mtb). We report the results of a preliminary structure-activity relationship (SAR) study of the compound class which has yielded more potent inhibitors. An Mtb cytochrome bd oxidase deletion mutant (cydKO) was found to be hypersensitive to most members of the compound library, while strains carrying single-nucleotide polymorphisms of the qcrB gene, which encodes a subunit of the menaquinol cytochrome c oxidoreductase (bc1) complex, were resistant to the library. These results identify that the 2-(quinolin-4-yloxy)acetamide class of Mtb growth inhibitors can be added to the growing number of scaffolds that target the M. tuberculosis bc1 complex.
2-(Quinolin-4-yloxy)acetamides Are Active against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains
Pissinate, Kenia,Villela, Anne Drumond,Rodrigues, Valnês,Giacobbo, Bruno Couto,Grams, Estêv?o Silveira,Abbadi, Bruno Lopes,Trindade, Rogério Valim,Roesler Nery, Laura,Bonan, Carla Denise,Back, Davi Fernando,Campos, Maria Martha,Basso, Luiz Augusto,Santos, Diógenes Santiago,Machado, Pablo
supporting information, p. 235 - 239 (2016/03/22)
2-(Quinolin-4-yloxy)acetamides have been described as potent in vitro inhibitors of Mycobacterium tuberculosis growth. Herein, additional chemical modifications of lead compounds were carried out, yielding highly potent antitubercular agents with minimum inhibitory concentration (MIC) values as low as 0.05 μM. Further, the synthesized compounds were active against drug-resistant strains and were devoid of apparent toxicity to Vero and HaCat cells (IC50s ≥ 20 μM). In addition, the 2-(quinolin-4-yloxy)acetamides showed intracellular activity against the bacilli in infected macrophages with action similar to rifampin, low risk of drug-drug interactions, and no sign of cardiac toxicity in zebrafish (Danio rerio) at 1 and 5 μM. Therefore, these data indicate that this class of compounds may furnish candidates for future development to, hopefully, provide drug alternatives for tuberculosis treatment.
Synthesis and cytotoxicity of thieno[2,3-b]pyridine and furo[2,3-b]pyridine derivatives
Hung, Joy M.,Arabshahi, Homayon J.,Leung, Euphemia,Reynisson, Jóhannes,Barker, David
, p. 420 - 437 (2015/02/19)
Forty seven thieno[2,3-b]pyridines-2-carboxamides, furo[2,3-b]pyridines-2-carboxamides and tetrahydrothieno[2,3-b]quinolones-2-carboxamides derivatives were synthesized and tested for their antiproliferative activity against the NCI-60 cell lines. The 5-keto-tetrahydrothieno[2,3-b]quinolones-2-carboxamides (series 17) were found to have the greatest activity, with the compound containing a 3-methoxyphenylcarboxamide (compound 17d) being the most active, with GI50values in the low nanomolar range against a range of cell lines, in particular the melanoma cell line MDA-MD-435 (GI50- 23 nM) and the breast cancer cell line MDA-MB-468 (GI50- 46 nM). Molecular modelling of series 17 against phosphoinositide specific-phospholipase C reveals that the side chains of the amino acids His356, Glu341, Arg549 and Lys438 are involved in hydrogen bonding with the ligands as well as a lipophilic pocket is occupied by the phenyl carboxamide moiety.
Synthesis, in vitro evaluation and cocrystal structure of 4-oxo-[1]benzopyrano[4,3-c]pyrazole cryptosporidium parvum inosine 5′-monophosphate dehydrogenase (Cp IMPDH) inhibitors
Sun, Zhuming,Khan, Jihan,Makowska-Grzyska, Magdalena,Zhang, Minjia,Cho, Joon Hyung,Suebsuwong, Chalada,Vo, Pascal,Gollapalli, Deviprasad R.,Kim, Youngchang,Joachimiak, Andrzej,Hedstrom, Lizbeth,Cuny, Gregory D.
supporting information, p. 10544 - 10550 (2015/02/19)
Cryptosporidium inosine 5′-monophosphate dehydrogenase (CpIMPDH) has emerged as a therapeutic target for treating Cryptosporidium parasites because it catalyzes a critical step in guanine nucleotide biosynthesis. A 4-oxo-[1]benzopyrano[4,3-c]pyrazole derivative was identified as a moderately potent (IC50 = 1.5 μM) inhibitor of CpIMPDH. We report a SAR study for this compound series resulting in 8k (IC50 = 20 ± 4 nM). In addition, an X-ray crystal structure of CpIMPDH·IMP·8k is also presented.
The convenient aqueous synthesis and biological evaluation of ortho-(3,4,5-trimethoxybenzoyl)-acetanilides as novel anti-cancer agents
Sheng, Jianfei,Mao, Fei,Yan, Jun,Huang, Ling,Li, Xingshu
, p. 41510 - 41520 (2014/12/11)
A series of new ortho-(3,4,5-trimethoxybenzoyl)-acetanilides were synthesised by the cross-coupling reaction catalyzed with Pd catalyst in aqueous medium, with polyethylene glycol as additive under very mild conditions. The evaluation of these compounds as tubulin polymerization inhibitors indicated that most of these compounds were potential anti-cancer agents. Among them, compound 13, 2-hydroxy-N-(5-methoxy-2-(3,4,5-trimethoxy benzoyl)phenyl) acetamide exhibited excellent antiproliferative activity against various human cancer cell lines (GI50= 71 nM for human HeLa cell line), and good activity for inhibiting tubulin polymerization (IC50= 2.94 μM). The mechanism study indicated that compound 13 could arrest cell-cycle progression at the mitosis phase, block the formation of cdc2/cyclin B1 complex, down-regulate the p-Cdc 25C and the anti-apoptotic proteins Bcl-2 and Bcl-XL, and up-regulate the pro-apoptotic proteins Bax and Bad. This journal is
