32428-61-8Relevant articles and documents
Synthesis and Biological Evaluation of Dithiobisacetamides as Novel Urease Inhibitors
Liu, Mei-Ling,Li, Wei-Yi,Fang, Hai-Lian,Ye, Ya-Xi,Li, Su-Ya,Song, Wan-Qing,Xiao, Zhu-Ping,Ouyang, Hui,Zhu, Hai-Liang
, (2021/11/13)
Thirty-eight disulfides containing N-arylacetamide were designed and synthesized in an effort to develop novel urease inhibitors. Biological evaluation revealed that some of the synthetic compounds exhibited strong inhibitory potency against both cell-free urease and urease in intact cell with low cytotoxicity to mammalian cells even at concentration up to 250 μM. Of note, 2,2′-dithiobis(N-(2-fluorophenyl)acetamide) (d7), 2,2′-dithiobis(N-(3,5-difluorophenyl)acetamide) (d24), and 2,2′-dithiobis(N-(3-fluorophenyl)acetamide) (d8) were here identified as the most active inhibitors with IC50 of 0.074, 0.44, and 0.81 μM, showing 32- to 355-fold higher potency than the positive control acetohydroxamic acid. These disulfides were confirmed to bind urease without covalent modification of the cysteine residue and to inhibit urease reversibly with a mixed inhibition mechanism. They also showed very good anti-Helicobacter pylori activities with d8 showing a comparable potency to the clinical used drug amoxicillin. The impressive in vitro biological profile indicated their immense potential as therapeutic agents to tackle H. pylori caused infections.
Synthesis of novel 1,2,3-triazoles bearing 2,4 thiazolidinediones conjugates and their biological evaluation
Kulkarni, Pravin S.,Karale, Sanjay N.,Khandebharad, Amol U.,Agrawal, Brijmohan R.,Sarda, Swapnil R.
, p. 2035 - 2046 (2021/02/05)
Searching for new active molecules against M. Bovis BCG and Mycobacterium tuberculosis (MTB) H37Ra, a focused of 1,2,3-triazoles-incorporated 2,4 thiazolidinedione conjugates have been efficiently prepared via a click chemistry approach cyclocondensation of 4-amino-N-(5-methylisoxazol-3-yl)benzenesulfonamide (4), aryl aldehyde (5a–l), and mercapto acetic acid (6) with good to promising yields. The newly synthesized compounds were tested against drug-sensitive MTB and BCG. In particular, compounds 8g, 8h, 8j and 8l are highly potent against both the strains with IC90 values in the range of 1.20–2.70 and 1.24–2.65?μg/mL, respectively. Based on the results from the antitubercular activity, SAR for the synthesized series has been developed. Most of the active compounds were non-cytotoxic against MCF-7, HCT 116 and A549 cell lines. Most active compounds were having a higher selectively index, which suggested that these compounds were highly potent.
Highly Potent and Selective Butyrylcholinesterase Inhibitors for Cognitive Improvement and Neuroprotection
Li, Qi,Chen, Ying,Xing, Shuaishuai,Liao, Qinghong,Xiong, Baichen,Wang, Yuanyuan,Lu, Weixuan,He, Siyu,Feng, Feng,Liu, Wenyuan,Chen, Yao,Sun, Haopeng
, p. 6856 - 6876 (2021/05/29)
Butyrylcholinesterase (BChE) has been considered as a potential therapeutic target for Alzheimer's disease (AD) because of its compensation capacity to hydrolyze acetylcholine (ACh) and its close association with Aβ deposit. Here, we identified S06-1011 (hBChE IC50 = 16 nM) and S06-1031 (hBChE IC50 = 25 nM) as highly effective and selective BChE inhibitors, which were proved to be safe and long-acting. Candidate compounds exhibited neuroprotective effects and the ability to improve cognition in scopolamine- and Aβ1-42 peptide-induced cognitive deficit models. The best candidate S06-1011 increased the level of ghrelin, a substrate of BChE, which can function as improving the mental mood appetite. The weight gain of the S06-1011-treated group remarkably increased. Hence, BChE inhibition not only plays a protective role against dementia but also exerts a great effect on treating and nursing care.
