132898-96-5Relevant articles and documents
Design, synthesis, molecular modeling, and antimicrobial potential of novel 3-[(1H-pyrazol-3-yl)imino]indolin-2-one derivatives as DNA gyrase inhibitors
Abu-Elghait, Mohammed,Alzahrani, Abdullah Y.,Ammar, Yousry A.,Ragab, Ahmed,Salem, Mohamed A.
, (2021/11/10)
A series of 3-[(1H-pyrazol-3-yl)imino]indolin-2-one derivatives were designed using the molecular hybridization method, characterized using different spectroscopic techniques, and evaluated for their in vitro antimicrobial activity. Most of the target compounds demonstrated good to moderate antimicrobial activity compared with ciprofloxacin and fluconazole. Four compounds (8b, 9a, 9c, and 10a) showed encouraging results, with minimal inhibitory concentration (MIC) values (53.45–258.32 μM) comparable to those of norfloxacin (100.31–200.63 μM) and ciprofloxacin (48.33–96.68 μM). Noticeably, the four derivatives revealed excellent bactericidal and fungicidal activities, except for the bacteriostatic potential of compounds 8b and 9a against Escherichia coli and Staphylococcus aureus, respectively. The time-killing kinetic study against S. aureus confirmed the efficacy of these derivatives. Furthermore, two of the four promising derivatives, 9a and 10a, could prevent the formation of biofilms of S. aureus without affecting the bacterial growth at low concentrations. A combination study with seven commercial antibiotics against the multidrug-resistant bacterium P. aeruginosa showed a notable reduction in the antibiotic MIC values, represented mainly through a synergistic or additive effect. The enzymatic assay implied that the most active derivatives had inhibition potency against DNA gyrase comparable to that of ciprofloxacin. Molecular docking and density functional theory calculations were performed to explore the binding mode and study the reactivity of the promising compounds.
Phenyl Benzenesulfonylhydrazides Exhibit Selective Indoleamine 2,3-Dioxygenase Inhibition with Potent in Vivo Pharmacodynamic Activity and Antitumor Efficacy
Lin, Shu-Yu,Yeh, Teng-Kuang,Kuo, Ching-Chuan,Song, Jen-Shin,Cheng, Ming-Fu,Liao, Fang-Yu,Chao, Min-Wu,Huang, Han-Li,Chen, Yi-Lin,Yang, Chun-Yu,Wu, Mine-Hsine,Hsieh, Chia-Ling,Hsiao, Wenchi,Peng, Yi-Hui,Wu, Jian-Sung,Lin, Li-Mei,Sun, Manwu,Chao, Yu-Sheng,Shih, Chuan,Wu, Su-Ying,Pan, Shiow-Lin,Hung, Ming-Shiu,Ueng, Shau-Hua
, p. 419 - 430 (2016/01/28)
Tryptophan metabolism has been recognized as an important mechanism in immune tolerance. Indoleamine 2,3-dioxygenase plays a key role in local tryptophan metabolism via the kynurenine pathway and has emerged as a therapeutic target for cancer immunotherapy. Our prior study identified phenyl benzenesulfonyl hydrazide 2 as a potent in vitro (though not in vivo) inhibitor of indoleamine 2,3-dioxygenase. Further lead optimization to improve in vitro potencies and pharmacokinetic profiles resulted in N′-(4-bromophenyl)-2-oxo-2,3-dihydro-1H-indole-5-sulfonyl hydrazide 40, which demonstrated 59% oral bioavailability and 73% of tumor growth delay without apparent body weight loss in the murine CT26 syngeneic model, after oral administration of 400 mg/kg. Accordingly, 40, is proposed as a potential drug lead worthy of advanced preclinical evaluation.
DERIVATIVES OF 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS
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Paragraph 0510, (2013/05/08)
Compounds, pyridine N-oxides, and pharmaceutically acceptable salts of formula (I) are useful as inhibitors of the phosphodiesterase 4 (PDE4) enzyme and for preventing and/ or treating diseases of the respiratory tract characterized by airway obstruction, such as asthma or COPD.
